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Current Diabetes Reviews

Editor-in-Chief

ISSN (Print): 1573-3998
ISSN (Online): 1875-6417

Review Article

Advancement in Understanding the Concept of Epithelial to Mesenchymal Transition in Pancreatic β-Cells: Implication in Diabetes

Author(s): Meenal Francis, Akshaya Ashok, Ashwini Ashwathnarayan, Shreetama Banerjee, Jyothi Prasanna and Anujith Kumar*

Volume 19, Issue 6, 2023

Published on: 10 November, 2022

Article ID: e190522205030 Pages: 17

DOI: 10.2174/1573399818666220519143414

Price: $65

Abstract

Distinct molecular processes are engaged during histogenesis, and Epithelial to Mesenchymal Transition (EMT) is one of the key evolutionarily conserved processes that facilitates organ development. Molecular pathways governing EMT are embedded within developmental programs and operate in cells of different tissues. Among varied cell types, EMT in pancreatic β-cells is of greater interest as the existence of EMT in these cells is highly debated. Although in vitro generation of human islet-derived mesenchymal progenitor cells has been proven beyond doubt, the existence of EMT in pancreatic β-cells in vivo remains enigmatic. Understanding the in-depth process of EMT in in vivo human β-cells is challenged by the limitations of lineage-tracing studies, which are otherwise feasible in mice. Exploring EMT of β-cells would greatly facilitate the generation of clinically relevant β-cells either by enhancing long-term in vitro culture of endogenous islets or by differentiation of pluripotent stem cells to mature β-cells. This review is an update on the recent progress in understanding the EMT process of β-cells and how the investigations have helped to resolve the mystery of the existence of EMT in pancreatic β-cells.

Keywords: Epithelial, Mesenchymal transition, EMT, Islets, Pancreatic β-cells, Diabetes, dedifferentiation

[1]
Galicia-Garcia U, Benito-Vicente A, Jebari S, et al. Pathophysiology of type 2 diabetes mellitus. Int J Mol Sci 2020; 21(17): 6275.
[http://dx.doi.org/10.3390/ijms21176275] [PMID: 32872570]
[2]
Cerf ME. Beta cell dysfunction and insulin resistance. Front Endocrinol (Lausanne) 2013; 4: 37.
[http://dx.doi.org/10.3389/fendo.2013.00037] [PMID: 23542897]
[3]
Giri B, Dey S, Das T, Sarkar M, Banerjee J, Dash SK. Chronic hyperglycemia mediated physiological alteration and metabolic distortion leads to organ dysfunction, infection, cancer progression and other pathophysiological consequences: An update on glucose toxicity. Biomed Pharmacother 2018; 107: 306-28.
[http://dx.doi.org/10.1016/j.biopha.2018.07.157] [PMID: 30098549]
[4]
Sumi S, Gu Y, Hiura A, Inoue K. Stem cells and regenerative medicine for diabetes mellitus. Pancreas 2004; 29(3): e85-9.
[http://dx.doi.org/10.1097/00006676-200410000-00017] [PMID: 15367898]
[5]
American Diabetes Association. Diagnosis and classification of diabetes mellitus. Diabetes Care 2013; 36 (Suppl. 1): S67-74.
[6]
Farney AC, Sutherland DE, Opara EC. Evolution of islet transplantation for the last 30 years. Pancreas 2016; 45(1): 8-20.
[http://dx.doi.org/10.1097/MPA.0000000000000391] [PMID: 26658037]
[7]
Sasaki H, Saisho Y, Inaishi J, Itoh H. Revisiting regulators of human β-cell mass to achieve β-cell-centric approach toward type 2 diabetes. J Endocr Soc 2021; 5(10): bvab128.
[8]
Butler AE, Janson J, Bonner-Weir S, Ritzel R, Rizza RA, Butler PC. β-cell deficit and increased β-cell apoptosis in humans with type 2 diabetes Diabetes 2003; 52(1): 102-10.
[http://dx.doi.org/10.2337/diabetes.52.1.102] [PMID: 12502499]
[9]
Jonas JC, Bensellam M, Duprez J, Elouil H, Guiot Y, Pascal SMA. Glucose regulation of islet stress responses and beta-cell failure in type 2 diabetes. Diabetes Obes Metab 2009; 11 (Suppl. 4): 65-81.
[http://dx.doi.org/10.1111/j.1463-1326.2009.01112.x] [PMID: 19817790]
[10]
Talchai C, Xuan S, Lin HV, Sussel L, Accili D. Pancreatic β cell dedifferentiation as a mechanism of diabetic β cell failure. Cell 2012; 150(6): 1223-34.
[http://dx.doi.org/10.1016/j.cell.2012.07.029] [PMID: 22980982]
[11]
Cinti F, Bouchi R, Kim-Muller JY, et al. Evidence of beta-cell dedifferentiation in human type 2 diabetes. J Clin Endocrinol Metab 2016; 101(3): 1044-54.
[http://dx.doi.org/10.1210/jc.2015-2860] [PMID: 26713822]
[12]
Sun T, Han X. Death versus dedifferentiation: The molecular bases of beta cell mass reduction in type 2 diabetes. Semin Cell Dev Biol 2020; 103: 76-82.
[http://dx.doi.org/10.1016/j.semcdb.2019.12.002] [PMID: 31831356]
[13]
Infeld DA, O’Shea JG. Diabetic retinopathy. Postgrad Med J 1998; 74(869): 129-33.
[http://dx.doi.org/10.1136/pgmj.74.869.129] [PMID: 9640436]
[14]
Air EL, Kissela BM. Diabetes, the metabolic syndrome, and ischemic stroke: Epidemiology and possible mechanisms. Diabetes Care 2007; 30(12): 3131-40.
[http://dx.doi.org/10.2337/dc06-1537] [PMID: 17848611]
[15]
Huo X, Gao L, Guo L, et al. Risk of non-fatal cardiovascular diseases in early-onset versus late-onset type 2 diabetes in China: A cross-sectional study. Lancet Diabetes Endocrinol 2016; 4(2): 115-24.
[http://dx.doi.org/10.1016/S2213-8587(15)00508-2] [PMID: 26704379]
[16]
Mariam TG, Alemayehu A, Tesfaye E, et al. Prevalence of diabetic foot ulcer and associated factors among adult diabetic patients who attend the diabetic follow-up clinic at the university of Gondar referral hospital, northwest Ethiopia, 2016: Institutional-based cross-sectional study. J Diabetes Res 2017; 2017: 2879249.
[http://dx.doi.org/10.1155/2017/2879249] [PMID: 28791310]
[17]
Shapiro AMJ, Lakey JRT, Ryan EA, et al. Islet transplantation in seven patients with type 1 diabetes mellitus using a glucocorticoid-free immunosuppressive regimen. N Engl J Med 2000; 343(4): 230-8.
[http://dx.doi.org/10.1056/NEJM200007273430401] [PMID: 10911004]
[18]
Sutherland DER, Gruessner R, Kandswamy R, Humar A, Hering B, Gruessner A. Beta-cell replacement therapy (pancreas and islet transplantation) for treatment of diabetes mellitus: an integrated approach. Transplant Proc 2004; 36(6): 1697-9.
[http://dx.doi.org/10.1016/j.transproceed.2004.06.069] [PMID: 15350456]
[19]
Bhonde RR, Sheshadri P, Sharma S, Kumar A. Making surrogate β-cells from mesenchymal stromal cells: Perspectives and future endeav-ors. Int J Biochem Cell Biol 2014; 46: 90-102.
[http://dx.doi.org/10.1016/j.biocel.2013.11.006] [PMID: 24275096]
[20]
Kaiser N, Corcos AP, Tur-Sinai A, Ariav Y, Cerasi E. Monolayer culture of adult rat pancreatic islets on extracellular matrix: Long term maintenance of differentiated B-cell function. Endocrinology 1988; 123(2): 834-40.
[http://dx.doi.org/10.1210/endo-123-2-834] [PMID: 2456205]
[21]
Hayek A, Lopez AD, Beattie GM. Enhancement of pancreatic islet cell monolayer growth by endothelial cell matrix and insulin. In Vitro Cell Dev Biol 1989; 25(2): 146-50.
[http://dx.doi.org/10.1007/BF02626171] [PMID: 2646271]
[22]
Hayek A, Beattie GM, Cirulli V, Lopez AD, Ricordi C, Rubin JS. Growth factor/matrix-induced proliferation of human adult beta-cells. Diabetes 1995; 44(12): 1458-60.
[http://dx.doi.org/10.2337/diab.44.12.1458] [PMID: 7589854]
[23]
Cornelius JG, Tchernev V, Kao KJ, Peck AB. In vitro-generation of islets in long-term cultures of pluripotent stem cells from adult mouse pancreas. Horm Metab Res 1997; 29(6): 271-7.
[http://dx.doi.org/10.1055/s-2007-979036] [PMID: 9230348]
[24]
Beattie GM, Lappi DA, Baird A, Hayek A. Selective elimination of fibroblasts from pancreatic islet monolayers by basic fibroblast growth factor-saporin mitotoxin. Diabetes 1990; 39(8): 1002-5.
[http://dx.doi.org/10.2337/diab.39.8.1002] [PMID: 2165003]
[25]
Gershengorn MC, Hardikar AA, Wei C, Geras-Raaka E, Marcus-Samuels B, Raaka BM. Epithelial-to-mesenchymal transition generates proliferative human islet precursor cells. Science 2004; 306(5705): 2261-4.
[http://dx.doi.org/10.1126/science.1101968] [PMID: 15564314]
[26]
Davani B, Ikonomou L, Raaka BM, et al. Human islet-derived precursor cells are mesenchymal stromal cells that differentiate and mature to hormone-expressing cells in vivo. Stem Cells 2007; 25(12): 3215-22.
[http://dx.doi.org/10.1634/stemcells.2007-0323] [PMID: 17901402]
[27]
Davani B, Ariely S, Ikonomou L, Oron Y, Gershengorn MC. Human islet-derived precursor cells can cycle between epithelial clusters and mesenchymal phenotypes. J Cell Mol Med 2009; 13(8B): 2570-81.
[http://dx.doi.org/10.1111/j.1582-4934.2008.00570.x] [PMID: 19175683]
[28]
Moreno-Amador JL, Téllez N, Marin S, et al. Epithelial to mesenchymal transition in human endocrine islet cells. PLoS One 2018; 13(1): e0191104.
[http://dx.doi.org/10.1371/journal.pone.0191104] [PMID: 29360826]
[29]
Atouf F, Park CH, Pechhold K, Ta M, Choi Y, Lumelsky NL. No evidence for mouse pancreatic beta-cell epithelial-mesenchymal transi-tion in vitro. Diabetes 2007; 56(3): 699-702.
[http://dx.doi.org/10.2337/db06-1446] [PMID: 17327438]
[30]
Chen J, Han Q, Pei D. EMT and MET as paradigms for cell fate switching. J Mol Cell Biol 2012; 4(2): 66-9.
[http://dx.doi.org/10.1093/jmcb/mjr045] [PMID: 22140271]
[31]
Nakaya Y, Sheng G. EMT in developmental morphogenesis. Cancer Lett 2013; 341(1): 9-15.
[http://dx.doi.org/10.1016/j.canlet.2013.02.037] [PMID: 23462225]
[32]
Lai X, Li Q, Wu F, et al. Epithelial-mesenchymal transition and metabolic switching in cancer: Lessons from somatic cell reprogramming. Front Cell Dev Biol 2020; 8: 760.
[http://dx.doi.org/10.3389/fcell.2020.00760] [PMID: 32850862]
[33]
López-Novoa JM, Nieto MA. Inflammation and EMT: An alliance towards organ fibrosis and cancer progression. EMBO Mol Med 2009; 1(6-7): 303-14.
[http://dx.doi.org/10.1002/emmm.200900043] [PMID: 20049734]
[34]
Lim J, Thiery JP. Epithelial-mesenchymal transitions: insights from development. Development 2012; 139(19): 3471-86.
[http://dx.doi.org/10.1242/dev.071209] [PMID: 22949611]
[35]
Amack JD. Cellular dynamics of EMT: Lessons from live in vivo imaging of embryonic development. Cell Commun Signal 2021; 19(1): 79.
[http://dx.doi.org/10.1186/s12964-021-00761-8] [PMID: 34294089]
[36]
Scheibner K, Schirge S, Burtscher I, et al. Epithelial cell plasticity drives endoderm formation during gastrulation. Nat Cell Biol 2021; 23(7): 692-703.
[http://dx.doi.org/10.1038/s41556-021-00694-x] [PMID: 34168324]
[37]
Davies JA, Garrod DR. Molecular aspects of the epithelial phenotype. BioEssays 1997; 19(8): 699-704.
[http://dx.doi.org/10.1002/bies.950190810] [PMID: 9264252]
[38]
Kalluri R, Weinberg RA. The basics of epithelial-mesenchymal transition. J Clin Invest 2009; 119(6): 1420-8.
[http://dx.doi.org/10.1172/JCI39104] [PMID: 19487818]
[39]
Bilder D, Schober M, Perrimon N. Integrated activity of PDZ protein complexes regulates epithelial polarity. Nat Cell Biol 2003; 5(1): 53-8.
[http://dx.doi.org/10.1038/ncb897] [PMID: 12510194]
[40]
Hurd TW, Gao L, Roh MH, Macara IG, Margolis B. Direct interaction of two polarity complexes implicated in epithelial tight junction assembly. Nat Cell Biol 2003; 5(2): 137-42.
[http://dx.doi.org/10.1038/ncb923] [PMID: 12545177]
[41]
Tanentzapf G, Tepass U. Interactions between the crumbs, lethal giant larvae and bazooka pathways in epithelial polarization. Nat Cell Biol 2003; 5(1): 46-52.
[http://dx.doi.org/10.1038/ncb896] [PMID: 12510193]
[42]
Whiteman EL, Liu CJ, Fearon ER, Margolis B. The transcription factor snail represses Crumbs3 expression and disrupts apico-basal po-larity complexes. Oncogene 2008; 27(27): 3875-9.
[http://dx.doi.org/10.1038/onc.2008.9] [PMID: 18246119]
[43]
Viloria-Petit AM, Wrana JL. The TGFbeta-Par6 polarity pathway: Linking the Par complex to EMT and breast cancer progression. Cell Cycle 2010; 9(4): 623-4.
[http://dx.doi.org/10.4161/cc.9.4.10779] [PMID: 20107326]
[44]
Lamouille S, Xu J, Derynck R. Molecular mechanisms of epithelial-mesenchymal transition. Nat Rev Mol Cell Biol 2014; 15(3): 178-96.
[http://dx.doi.org/10.1038/nrm3758] [PMID: 24556840]
[45]
Lee K, Nelson CM. New insights into the regulation of epithelial-mesenchymal transition and tissue fibrosis. Int Rev Cell Mol Biol 2012; 294: 171-221.
[http://dx.doi.org/10.1016/B978-0-12-394305-7.00004-5] [PMID: 22364874]
[46]
Jung AR, Jung C-H, Noh JK, Lee YC, Eun YG. Epithelial-mesenchymal transition gene signature is associated with prognosis and tumor microenvironment in head and neck squamous cell carcinoma. Sci Rep 2020; 10(1): 3652.
[http://dx.doi.org/10.1038/s41598-020-60707-x] [PMID: 32107458]
[47]
Wang H, Wang H-S, Zhou B-H, et al. Epithelial-Mesenchymal Transition (EMT) induced by TNF-α requires AKT/GSK-3β-mediated stabilization of snail in colorectal cancer. PLoS One 2013; 8(2): e56664.
[http://dx.doi.org/10.1371/journal.pone.0056664] [PMID: 23431386]
[48]
Skrypek N, Goossens S, De Smedt E, Vandamme N, Berx G. Epithelial-to-mesenchymal transition: Epigenetic reprogramming driving cellular plasticity. Trends Genet 2017; 33(12): 943-59.
[http://dx.doi.org/10.1016/j.tig.2017.08.004] [PMID: 28919019]
[49]
Serrano-Gomez SJ, Maziveyi M, Alahari SK. Regulation of epithelial-mesenchymal transition through epigenetic and post-translational modifications. Mol Cancer 2016; 15(1): 18.
[http://dx.doi.org/10.1186/s12943-016-0502-x] [PMID: 26905733]
[50]
Dong B, Qiu Z, Wu Y. Tackle epithelial-mesenchymal transition with epigenetic drugs in cancer. Front Pharmacol 2020; 11: 596239.
[http://dx.doi.org/10.3389/fphar.2020.596239] [PMID: 33343366]
[51]
Title AC, Hong S-J, Pires ND, et al. Genetic dissection of the miR-200-Zeb1 axis reveals its importance in tumor differentiation and invasion. Nat Commun 2018; 9(1): 4671.
[http://dx.doi.org/10.1038/s41467-018-07130-z] [PMID: 30405106]
[52]
Grieco GE, Brusco N, Licata G, et al. The landscape of microRNAs in βcell: Between phenotype maintenance and protection. Int J Mol Sci 2021; 22(2): 803.
[http://dx.doi.org/10.3390/ijms22020803] [PMID: 33466949]
[53]
Montgomery AM, Yebra M. The epithelial-to-mesenchymal transition of human pancreatic β-cells: Inductive mechanisms and implications for the cell-based therapy of type I diabetes. Curr Diabetes Rev 2011; 7(5): 346-55.
[http://dx.doi.org/10.2174/157339911797415639] [PMID: 21916835]
[54]
Chen C-M, Juan S-H, Pai M-H, Chou HC. Hyperglycemia induces epithelial-mesenchymal transition in the lungs of experimental diabetes mellitus. Acta Histochem 2018; 120(6): 525-33.
[http://dx.doi.org/10.1016/j.acthis.2018.06.004] [PMID: 29934127]
[55]
Joglekar MV, Hardikar AA. Epithelial-to-mesenchymal transition in pancreatic islet beta cells. Cell Cycle 2010; 9(20): 4077-9.
[http://dx.doi.org/10.4161/cc.9.20.13590] [PMID: 20948307]
[56]
Talchai C, Xuan S, Kitamura T, DePinho RA, Accili D. Generation of functional insulin-producing cells in the gut by Foxo1 ablation. Nat Genet 2012; 44(4): 406-12.
[http://dx.doi.org/10.1038/ng.2215]
[57]
Roefs MM, Carlotti F, Jones K, et al. Increased vimentin in human α- and β-cells in type 2 diabetes. J Endocrinol 2017; 233(3): 217-27.
[http://dx.doi.org/10.1530/JOE-16-0588] [PMID: 28348116]
[58]
Efrat S. Beta-cell dedifferentiation in type 2 diabetes: Concise review. Stem Cells 2019; 37(10): 1267-72.
[http://dx.doi.org/10.1002/stem.3059] [PMID: 31298804]
[59]
Khin PP, Lee JH, Jun HS. A brief review of the mechanisms of β-cell dedifferentiation in type 2 diabetes. Nutrients 2021; 13(5): 1593.
[http://dx.doi.org/10.3390/nu13051593] [PMID: 34068827]
[60]
Puri S, Hebrok M. Cellular plasticity within the pancreas--lessons learned from development. Dev Cell 2010; 18(3): 342-56.
[http://dx.doi.org/10.1016/j.devcel.2010.02.005] [PMID: 20230744]
[61]
McKnight KD, Wang P, Kim SK. Deconstructing pancreas development to reconstruct human islets from pluripotent stem cells. Cell Stem Cell 2010; 6(4): 300-8.
[http://dx.doi.org/10.1016/j.stem.2010.03.003] [PMID: 20362535]
[62]
Offield MF, Jetton TL, Labosky PA, et al. PDX-1 is required for pancreatic outgrowth and differentiation of the rostral duodenum. Development 1996; 122(3): 983-95.
[http://dx.doi.org/10.1242/dev.122.3.983] [PMID: 8631275]
[63]
Pictet RL, Clark WR, Williams RH, Rutter WJ. An ultrastructural analysis of the developing embryonic pancreas. Dev Biol 1972; 29(4): 436-67.
[http://dx.doi.org/10.1016/0012-1606(72)90083-8] [PMID: 4570759]
[64]
Slack JM. Developmental biology of the pancreas. Development 1995; 121(6): 1569-80.
[http://dx.doi.org/10.1242/dev.121.6.1569] [PMID: 7600975]
[65]
Kim SK, MacDonald RJ. Signaling and transcriptional control of pancreatic organogenesis. Curr Opin Genet Dev 2002; 12(5): 540-7.
[http://dx.doi.org/10.1016/S0959-437X(02)00338-6] [PMID: 12200159]
[66]
Bilyk O, Coatham M, Jewer M, Postovit LM. Epithelial-to-mesenchymal transition in the female reproductive tract: From normal function-ing to disease pathology. Front Oncol 2017; 7: 145.
[http://dx.doi.org/10.3389/fonc.2017.00145] [PMID: 28725636]
[67]
Hashimoto K, Nakatsuji N. Formation of the primitive streak and mesoderm cells in mouse embryos-detailed scanning electron micro-scopical study. Dev Growth Differ 1989; 31(3): 209-18.
[http://dx.doi.org/10.1111/j.1440-169X.1989.00209.x]
[68]
Ferrer-Vaquer A, Viotti M, Hadjantonakis AK. Transitions between epithelial and mesenchymal states and the morphogenesis of the early mouse embryo. Cell Adhes Migr 2010; 4(3): 447-57.
[http://dx.doi.org/10.4161/cam.4.3.10771] [PMID: 20200481]
[69]
Nakaya Y, Sheng G. Epithelial to mesenchymal transition during gastrulation: An embryological view. Dev Growth Differ 2008; 50(9): 755-66.
[http://dx.doi.org/10.1111/j.1440-169X.2008.01070.x] [PMID: 19046163]
[70]
Nieto MA, Sargent MG, Wilkinson DG, Cooke J. Control of cell behavior during vertebrate development by Slug, a zinc finger gene. Science 1994; 264(5160): 835-9.
[http://dx.doi.org/10.1126/science.7513443] [PMID: 7513443]
[71]
Sun X, Meyers EN, Lewandoski M, Martin GR. Targeted disruption of Fgf8 causes failure of cell migration in the gastrulating mouse embryo. Genes Dev 1999; 13(14): 1834-46.
[http://dx.doi.org/10.1101/gad.13.14.1834] [PMID: 10421635]
[72]
Carver EA, Jiang R, Lan Y, Oram KF, Gridley T. The mouse snail gene encodes a key regulator of the epithelial-mesenchymal transition. Mol Cell Biol 2001; 21(23): 8184-8.
[http://dx.doi.org/10.1128/MCB.21.23.8184-8188.2001] [PMID: 11689706]
[73]
Thiery JP, Acloque H, Huang RY, Nieto MA. Epithelial-mesenchymal transitions in development and disease. Cell 2009; 139(5): 871-90.
[http://dx.doi.org/10.1016/j.cell.2009.11.007] [PMID: 19945376]
[74]
Papaioannou VE. The T-box gene family: Emerging roles in development, stem cells and cancer. Development 2014; 141(20): 3819-33.
[http://dx.doi.org/10.1242/dev.104471] [PMID: 25294936]
[75]
Ramkumar N, Omelchenko T, Silva-Gagliardi NF, McGlade CJ, Wijnholds J, Anderson KV. Crumbs2 promotes cell ingression during the epithelial-to-mesenchymal transition at gastrulation. Nat Cell Biol 2016; 18(12): 1281-91.
[http://dx.doi.org/10.1038/ncb3442] [PMID: 27870829]
[76]
Bazzi H, Soroka E, Alcorn HL, Anderson KV. STRIP1, a core component of STRIPAK complexes, is essential for normal mesoderm migration in the mouse embryo. Proc Natl Acad Sci USA 2017; 114(51): E10928-36.
[http://dx.doi.org/10.1073/pnas.1713535114] [PMID: 29203676]
[77]
Hebrok M, Kim SK, Melton DA. Notochord repression of endodermal Sonic hedgehog permits pancreas development. Genes Dev 1998; 12(11): 1705-13.
[http://dx.doi.org/10.1101/gad.12.11.1705] [PMID: 9620856]
[78]
Johansson KA, Grapin-Botton A. Development and diseases of the pancreas. Clin Genet 2002; 62(1): 14-23.
[http://dx.doi.org/10.1034/j.1399-0004.2002.620102.x] [PMID: 12123481]
[79]
Pan FC, Wright C. Pancreas organogenesis: From bud to plexus to gland. Dev Dyn 2011; 240(3): 530-65.
[http://dx.doi.org/10.1002/dvdy.22584] [PMID: 21337462]
[80]
Deutsch G, Jung J, Zheng M, Lóra J. Zaret KS. A bipotential precursor population for pancreas and liver within the embryonic endoderm. Development 2001; 128(6): 871-81.
[http://dx.doi.org/10.1242/dev.128.6.871] [PMID: 11222142]
[81]
Jensen J, Heller RS, Funder-Nielsen T, et al. Independent development of pancreatic alpha- and beta-cells from neurogenin3-expressing precursors: A role for the notch pathway in repression of premature differentiation. Diabetes 2000; 49(2): 163-76.
[http://dx.doi.org/10.2337/diabetes.49.2.163] [PMID: 10868931]
[82]
Gu G, Dubauskaite J, Melton DA. Direct evidence for the pancreatic lineage: NGN3+ cells are islet progenitors and are distinct from duct progenitors. Development 2002; 129(10): 2447-57.
[http://dx.doi.org/10.1242/dev.129.10.2447] [PMID: 11973276]
[83]
Gu G, Brown JR, Melton DA. Direct lineage tracing reveals the ontogeny of pancreatic cell fates during mouse embryogenesis. Mech Dev 2003; 120(1): 35-43.
[http://dx.doi.org/10.1016/S0925-4773(02)00330-1] [PMID: 12490294]
[84]
Rukstalis JM, Habener JF. Snail2, a mediator of epithelial-mesenchymal transitions, expressed in progenitor cells of the developing endo-crine pancreas. Gene Expr Patterns 2007; 7(4): 471-9.
[http://dx.doi.org/10.1016/j.modgep.2006.11.001] [PMID: 17185046]
[85]
Cole L, Anderson M, Antin PB, Limesand SW. One process for pancreatic β-cell coalescence into islets involves an epithelial-mesenchymal transition. J Endocrinol 2009; 203(1): 19-31.
[http://dx.doi.org/10.1677/JOE-09-0072] [PMID: 19608613]
[86]
Gouzi M, Kim YH, Katsumoto K, Johansson K, Grapin-Botton A. Neurogenin3 initiates stepwise delamination of differentiating endocrine cells during pancreas development. Dev Dyn 2011; 240(3): 589-604.
[http://dx.doi.org/10.1002/dvdy.22544] [PMID: 21287656]
[87]
Chiang MK, Melton DA. Single-cell transcript analysis of pancreas development. Dev Cell 2003; 4(3): 383-93.
[http://dx.doi.org/10.1016/S1534-5807(03)00035-2] [PMID: 12636919]
[88]
Parnaud G, Lavallard V, Bedat B, et al. Cadherin engagement improves insulin secretion of single human β-cells. Diabetes 2015; 64(3): 887-96.
[http://dx.doi.org/10.2337/db14-0257] [PMID: 25277393]
[89]
Avrahami D, Wang YJ, Schug J, et al. Single-cell transcriptomics of human islet ontogeny defines the molecular basis of β-cell dedifferentiation in T2D. Mol Metab 2020; 42: 101057.
[http://dx.doi.org/10.1016/j.molmet.2020.101057] [PMID: 32739450]
[90]
Ramiya VK, Maraist M, Arfors KE, Schatz DA, Peck AB, Cornelius JG. Reversal of insulin-dependent diabetes using islets generated in vitro from pancreatic stem cells. Nat Med 2000; 6(3): 278-82.
[http://dx.doi.org/10.1038/73128] [PMID: 10700229]
[91]
Zulewski H, Abraham EJ, Gerlach MJ, et al. Multipotential nestin-positive stem cells isolated from adult pancreatic islets differentiate ex vivo into pancreatic endocrine, exocrine, and hepatic phenotypes. Diabetes 2001; 50(3): 521-33.
[http://dx.doi.org/10.2337/diabetes.50.3.521] [PMID: 11246871]
[92]
Morton RA, Geras-Raaka E, Wilson LM, Raaka BM, Gershengorn MC. Endocrine precursor cells from mouse islets are not generated by epithelial-to-mesenchymal transition of mature beta cells. Mol Cell Endocrinol 2007; 270(1-2): 87-93.
[http://dx.doi.org/10.1016/j.mce.2007.02.005] [PMID: 17363142]
[93]
Weinberg N, Ouziel-Yahalom L, Knoller S, Efrat S, Dor Y. Lineage tracing evidence for in vitro dedifferentiation but rare proliferation of mouse pancreatic beta-cells. Diabetes 2007; 56(5): 1299-304.
[http://dx.doi.org/10.2337/db06-1654] [PMID: 17303800]
[94]
Chase LG, Ulloa-Montoya F, Kidder BL, Verfaillie CM. Islet-derived fibroblast-like cells are not derived via epithelial-mesenchymal tran-sition from Pdx-1 or insulin-positive cells. Diabetes 2007; 56(1): 3-7.
[http://dx.doi.org/10.2337/db06-1165] [PMID: 17110468]
[95]
Guy LG, Kothary R, Wall L. Position effects in mice carrying a lacZ transgene in cis with the beta-globin LCR can be explained by a graded model. Nucleic Acids Res 1997; 25(21): 4400-7.
[http://dx.doi.org/10.1093/nar/25.21.4400] [PMID: 9336475]
[96]
Jolly MK, Boareto M, Huang B, et al. Implications of the hybrid epithelial/mesenchymal phenotype in metastasis. Front Oncol 2015; 5: 155.
[http://dx.doi.org/10.3389/fonc.2015.00155] [PMID: 26258068]
[97]
Nimkulrat SD, Bernstein MN, Ni Z, Brown J, Kendziorski C, Blum B. The Anna Karenina model of β-cell maturation in development and their dedifferentiation in type 1 and type 2 diabetes. Diabetes 2021; 70(9): 2058-66.
[http://dx.doi.org/10.2337/db21-0211] [PMID: 34417264]
[98]
Xiao X, Fischbach S, Zhang T, et al. SMAD3/Stat3 signaling mediates β-cell epithelial-mesenchymal transition in chronic pancreatitis–related diabetes. Diabetes 2017; 66(10): 2646-58.
[http://dx.doi.org/10.2337/db17-0537] [PMID: 28775125]
[99]
Heinis M, Simon MT, Ilc K, et al. Oxygen tension regulates pancreatic beta-cell differentiation through hypoxia-inducible factor 1alpha. Diabetes 2010; 59(3): 662-9.
[http://dx.doi.org/10.2337/db09-0891] [PMID: 20009089]
[100]
Liu N, Cai X, Liu T, et al. Hypoxia-inducible factor-1α mediates the expression of mature β cell-disallowed genes in hypoxia-induced β cell dedifferentiation. Biochem Biophys Res Commun 2020; 523(2): 382-8.
[http://dx.doi.org/10.1016/j.bbrc.2019.12.063] [PMID: 31866014]
[101]
Pascal SM, Guiot Y, Pelengaris S, Khan M, Jonas JC. Effects of c-MYC activation on glucose stimulus-secretion coupling events in mouse pancreatic islets. Am J Physiol Endocrinol Metab 2008; 295(1): E92-E102.
[http://dx.doi.org/10.1152/ajpendo.90235.2008] [PMID: 18413670]
[102]
Bensellam M, Jonas J-C, Laybutt DR. Mechanisms of β-cell dedifferentiation in diabetes: Recent findings and future research directions. J Endocrinol 2018; 236(2): R109-43.
[http://dx.doi.org/10.1530/JOE-17-0516] [PMID: 29203573]
[103]
Ježek P, Jabůrek M, Plecitá-Hlavatá L. Contribution of oxidative stress and impaired biogenesis of pancreatic β-cells to type 2 diabetes. Antioxid Redox Signal 2019; 31(10): 722-51.
[http://dx.doi.org/10.1089/ars.2018.7656] [PMID: 30450940]
[104]
Benáková Š, Holendová B, Plecitá-Hlavatá L. Redox homeostasis in pancreatic β-cells: From development to failure. Antioxidants 2021; 10(4): 526.
[http://dx.doi.org/10.3390/antiox10040526] [PMID: 33801681]
[105]
Bilekova S, Sachs S, Lickert H. Pharmacological targeting of endoplasmic reticulum stress in pancreatic beta cells. Trends Pharmacol Sci 2021; 42(2): 85-95.
[http://dx.doi.org/10.1016/j.tips.2020.11.011] [PMID: 33353789]
[106]
Zhang J, An H, Ni K, et al. Glutathione prevents chronic oscillating glucose intake-induced β-cell dedifferentiation and failure. Cell Death Dis 2019; 10(4): 321.
[http://dx.doi.org/10.1038/s41419-019-1552-y] [PMID: 30975975]
[107]
Kitamura YI, Kitamura T, Kruse JP, et al. FoxO1 protects against pancreatic β cell failure through NeuroD and MafA induction. Cell Metab 2005; 2(3): 153-63.
[http://dx.doi.org/10.1016/j.cmet.2005.08.004] [PMID: 16154098]
[108]
Dumayne C, Tarussio D, Sanchez-Archidona AR, et al. Klf6 protects β-cells against insulin resistance-induced dedifferentiation. Mol Metab 2020; 35: 100958.
[http://dx.doi.org/10.1016/j.molmet.2020.02.001] [PMID: 32244185]
[109]
Mak TCS, Ohlen YV, Wang YF, et al. β-cell dedifferentiation is associated with epithelial-mesenchymal transition triggered by miR-7-mediated repression of mSwi/Snf complex. bioRxiv 2019; 789461.
[http://dx.doi.org/10.1101/789461]
[110]
de Jesus DS, Mak TCS, Wang Y-F, et al. Dysregulation of the Pdx1/Ovol2/Zeb2 axis in dedifferentiated β-cells triggers the induction of genes associated with epithelial-mesenchymal transition in diabetes. Mol Metab 2021; 53: 101248.
[http://dx.doi.org/10.1016/j.molmet.2021.101248] [PMID: 33989778]
[111]
Ibrahim S, Johnson M, Stephens CH, et al. β-Cell pre-mir-21 induces dysfunction and loss of cellular identity by targeting transforming growth factor beta 2 (Tgfb2) and Smad family member 2 (Smad2) mRNAs. Mol Metab 2021; 53: 101289.
[http://dx.doi.org/10.1016/j.molmet.2021.101289] [PMID: 34246804]
[112]
Gallo R, Gambelli F, Gava B, et al. Generation and expansion of multipotent mesenchymal progenitor cells from cultured human pancreatic islets. Cell Death Differ 2007; 14(11): 1860-71.
[http://dx.doi.org/10.1038/sj.cdd.4402199] [PMID: 17612586]
[113]
Eberhardt M, Salmon P, von Mach M-A, et al. Multipotential nestin and Isl-1 positive mesenchymal stem cells isolated from human pancreatic islets. Biochem Biophys Res Commun 2006; 345(3): 1167-76.
[http://dx.doi.org/10.1016/j.bbrc.2006.05.016] [PMID: 16713999]
[114]
Huang H, Tang X. Phenotypic determination and characterization of nestin-positive precursors derived from human fetal pancreas. Lab Invest 2003; 83(4): 539-47.
[http://dx.doi.org/10.1097/01.LAB.0000062890.40534.1C] [PMID: 12695557]
[115]
Abraham EJ, Leech CA, Lin JC, Zulewski H, Habener JF. Insulinotropic hormone glucagon-like peptide-1 differentiation of human pancreatic islet-derived progenitor cells into insulin-producing cells. Endocrinology 2002; 143(8): 3152-61.
[http://dx.doi.org/10.1210/endo.143.8.8973] [PMID: 12130581]
[116]
Russ HA, Bar Y, Ravassard P, Efrat S. In vitro proliferation of cells derived from adult human beta-cells revealed by cell-lineage tracing. Diabetes 2008; 57(6): 1575-83.
[http://dx.doi.org/10.2337/db07-1283] [PMID: 18316362]
[117]
Russ HA, Ravassard P, Kerr-Conte J, Pattou F, Efrat S. Epithelial-mesenchymal transition in cells expanded in vitro from lineage-traced adult human pancreatic beta cells. PLoS One 2009; 4(7): e6417.
[http://dx.doi.org/10.1371/journal.pone.0006417] [PMID: 19641613]
[118]
Limbert C, Ebert R, Schilling T, et al. Functional signature of human islet-derived precursor cells compared to bone marrow-derived mesenchymal stem cells. Stem Cells Dev 2010; 19(5): 679-91.
[http://dx.doi.org/10.1089/scd.2009.0241] [PMID: 19895235]
[119]
Russ HA, Sintov E, Anker-Kitai L, et al. Insulin-producing cells generated from dedifferentiated human pancreatic beta cells expanded in vitro. PLoS One 2011; 6(9): e25566.
[http://dx.doi.org/10.1371/journal.pone.0025566] [PMID: 21984932]
[120]
Friedman-Mazursky O, Elkon R, Efrat S. Redifferentiation of expanded human islet β cells by inhibition of ARX. Sci Rep 2016; 6(1): 20698.
[http://dx.doi.org/10.1038/srep20698] [PMID: 26856418]
[121]
Nathan G, Kredo-Russo S, Geiger T, et al. MiR-375 promotes redifferentiation of adult human β cells expanded in vitro. PLoS One 2015; 10(4): e0122108.
[http://dx.doi.org/10.1371/journal.pone.0122108] [PMID: 25875172]
[122]
Wang Z, York NW, Nichols CG, Remedi MS. Pancreatic β cell dedifferentiation in diabetes and redifferentiation following insulin therapy. Cell Metab 2014; 19(5): 872-82.
[http://dx.doi.org/10.1016/j.cmet.2014.03.010] [PMID: 24746806]
[123]
Seeberger KL, Eshpeter A, Rajotte RV, Korbutt GS. Epithelial cells within the human pancreas do not coexpress mesenchymal antigens: Epithelial-mesenchymal transition is an artifact of cell culture. Lab Invest 2009; 89(2): 110-21.
[http://dx.doi.org/10.1038/labinvest.2008.122] [PMID: 19079324]
[124]
Sheng C, Li F, Lin Z, et al. Reversibility of β-cell-specific transcript factors expression by long-term caloric restriction in db/db Mouse. J Diabetes Res 2016; 2016: 6035046.
[http://dx.doi.org/10.1155/2016/6035046] [PMID: 26998492]
[125]
Csóka B, Törő G, Vindeirinho J, et al. A2A adenosine receptors control pancreatic dysfunction in high-fat-diet-induced obesity. FASEB J 2017; 31(11): 4985-97.
[http://dx.doi.org/10.1096/fj.201700398R] [PMID: 28765173]
[126]
Latreille M, Hausser J, Stützer I, et al. MicroRNA-7a regulates pancreatic β cell function. J Clin Invest 2014; 124(6): 2722-35.
[http://dx.doi.org/10.1172/JCI73066] [PMID: 24789908]
[127]
Fiori JL, Shin YK, Kim W, et al. Resveratrol prevents β-cell dedifferentiation in nonhuman primates given a high-fat/high-sugar diet. Diabetes 2013; 62(10): 3500-13.
[http://dx.doi.org/10.2337/db13-0266] [PMID: 23884882]
[128]
Belongie KJ, Ferrannini E, Johnson K, Andrade-Gordon P, Hansen MK, Petrie JR. Identification of novel biomarkers to monitor β-cell function and enable early detection of type 2 diabetes risk. PLoS One 2017; 12(8): e0182932.
[http://dx.doi.org/10.1371/journal.pone.0182932] [PMID: 28846711]
[129]
Valdez IA, Dirice E, Gupta MK, Shirakawa J, Teo AKK, Kulkarni RN. Proinflammatory cytokines induce endocrine differentiation in pancreatic ductal cells via stat3-dependent NGN3 activation. Cell Rep 2016; 15(3): 460-70.
[http://dx.doi.org/10.1016/j.celrep.2016.03.036] [PMID: 27068459]
[130]
Corritore E, Dugnani E, Pasquale V, et al. β-Cell differentiation of human pancreatic duct-derived cells after in vitro expansion. Cell Reprogram 2014; 16(6): 456-66.
[http://dx.doi.org/10.1089/cell.2014.0025] [PMID: 25437872]
[131]
Lima MJ, Muir KR, Docherty HM, et al. Suppression of epithelial-to-mesenchymal transitioning enhances ex vivo reprogramming of human exocrine pancreatic tissue toward functional insulin-producing β-like cells. Diabetes 2013; 62(8): 2821-33.
[http://dx.doi.org/10.2337/db12-1256] [PMID: 23610058]
[132]
Lee H, Lee YS, Harenda Q, et al. Beta cell dedifferentiation induced by IRE1α deletion prevents type 1 diabetes. Cell Metab 2020; 31(4): 822-836.e5.
[http://dx.doi.org/10.1016/j.cmet.2020.03.002] [PMID: 32220307]
[133]
Weir GC, Aguayo-Mazzucato C, Bonner-Weir S. β-cell dedifferentiation in diabetes is important, but what is it? Islets 2013; 5(5): 233-7.
[http://dx.doi.org/10.4161/isl.27494] [PMID: 24356710]
[134]
Zhu Y, Sun Y, Zhou Y, et al. MicroRNA-24 promotes pancreatic beta cells toward dedifferentiation to avoid endoplasmic reticulum stress-induced apoptosis. J Mol Cell Biol 2019; 11(9): 747-60.
[http://dx.doi.org/10.1093/jmcb/mjz004] [PMID: 30753517]
[135]
Kulkarni RN, Mizrachi EB, Ocana AG, Stewart AF. Human β-cell proliferation and intracellular signaling: Driving in the dark without a road map. Diabetes 2012; 61(9): 2205-13.
[http://dx.doi.org/10.2337/db12-0018] [PMID: 22751699]
[136]
Puddu A, Sanguineti R, Mach F, Dallegri F, Viviani GL, Montecucco F. Update on the protective molecular pathways improving pancreatic beta-cell dysfunction. Mediators Inflamm 2013; 2013: 750540.
[http://dx.doi.org/10.1155/2013/750540] [PMID: 23737653]
[137]
Jiang W-J, Peng Y-C, Yang K-M. Cellular signaling pathways regulating β-cell proliferation as a promising therapeutic target in the treatment of diabetes. Exp Ther Med 2018; 16(4): 3275-85.
[http://dx.doi.org/10.3892/etm.2018.6603] [PMID: 30233674]
[138]
Gonzalez DM, Medici D. Signaling mechanisms of the epithelial-mesenchymal transition. Sci Signal 2014; 7(344): re8.
[http://dx.doi.org/10.1126/scisignal.2005189] [PMID: 25249658]
[139]
Bosco D, Rouiller DG, Halban PA. Differential expression of E-cadherin at the surface of rat β-cells as a marker of functional heterogeneity. J Endocrinol 2007; 194(1): 21-9.
[http://dx.doi.org/10.1677/JOE-06-0169] [PMID: 17592017]
[140]
Rogers GJ, Hodgkin MN, Squires PE. E-cadherin and cell adhesion: A role in architecture and function in the pancreatic islet. Cell Physiol Biochem 2007; 20(6): 987-94.
[http://dx.doi.org/10.1159/000110459] [PMID: 17982281]
[141]
Banerjee M, Virtanen I, Palgi J, Korsgren O, Otonkoski T. Proliferation and plasticity of human beta cells on physiologically occurring laminin isoforms. Mol Cell Endocrinol 2012; 355(1): 78-86.
[http://dx.doi.org/10.1016/j.mce.2012.01.020] [PMID: 22314207]
[142]
Xu J, Lamouille S, Derynck R. TGF-β-induced epithelial to mesenchymal transition. Cell Res 2009; 19(2): 156-72.
[http://dx.doi.org/10.1038/cr.2009.5] [PMID: 19153598]
[143]
Kim BN, Ahn DH, Kang N, et al. TGF-β-induced EMT and stemness characteristics are associated with epigenetic regulation in lung can-cer. Sci Rep 2020; 10(1): 10597.
[http://dx.doi.org/10.1038/s41598-020-67325-7] [PMID: 32606331]
[144]
Lee J-H, Lee J-H, Rane SG. TGF-β signaling in pancreatic islet β cell development and function. Endocrinology 2021; 162(3): bqaa233.
[145]
Dhawan S, Dirice E, Kulkarni RN, Bhushan A. Inhibition of TGF-β signaling promotes human pancreatic β-cell replication. Diabetes 2016; 65(5): 1208-18.
[http://dx.doi.org/10.2337/db15-1331] [PMID: 26936960]
[146]
Blum B, Roose AN, Barrandon O, et al. Reversal of β cell dedifferentiation by a small molecule inhibitor of the TGFβ pathway. eLife 2014; 3: e02809.
[http://dx.doi.org/10.7554/eLife.02809] [PMID: 25233132]
[147]
Bertolino P, Holmberg R, Reissmann E, Andersson O, Berggren PO, Ibáñez CF. Activin B receptor ALK7 is a negative regulator of pancre-atic β-cell function. Proc Natl Acad Sci USA 2008; 105(20): 7246-51.
[http://dx.doi.org/10.1073/pnas.0801285105] [PMID: 18480258]
[148]
Smart NG, Apelqvist AA, Gu X, et al. Conditional expression of Smad7 in pancreatic beta cells disrupts TGF-beta signaling and induces reversible diabetes mellitus. PLoS Biol 2006; 4(2): e39.
[http://dx.doi.org/10.1371/journal.pbio.0040039] [PMID: 16435884]
[149]
Brown ML, Schneyer AL. Emerging roles for the TGFbeta family in pancreatic beta-cell homeostasis. Trends Endocrinol Metab 2010; 21(7): 441-8.
[http://dx.doi.org/10.1016/j.tem.2010.02.008] [PMID: 20382030]
[150]
Toren-Haritan G, Efrat S. TGFβ pathway inhibition redifferentiates human pancreatic islet β cells expanded in vitro. PLoS One 2015; 10(9): e0139168.
[http://dx.doi.org/10.1371/journal.pone.0139168] [PMID: 26418361]
[151]
El-Gohary Y, Tulachan S, Guo P, et al. Smad signaling pathways regulate pancreatic endocrine development. Dev Biol 2013; 378(2): 83-93.
[http://dx.doi.org/10.1016/j.ydbio.2013.04.003] [PMID: 23603491]
[152]
Xiao X, Gaffar I, Guo P, et al. M2 macrophages promote beta-cell proliferation by up-regulation of SMAD7. Proc Natl Acad Sci USA 2014; 111(13): E1211-20.
[http://dx.doi.org/10.1073/pnas.1321347111] [PMID: 24639504]
[153]
Lee J-H, Mellado-Gil JM, Bahn YJ, Pathy SM, Zhang YE, Rane SG. Protection from β-cell apoptosis by inhibition of TGF-β/Smad3 signaling. Cell Death Dis 2020; 11(3): 184.
[http://dx.doi.org/10.1038/s41419-020-2365-8] [PMID: 32170115]
[154]
Shrestha N, Liu T, Ji Y, et al. Sel1L-Hrd1 ER-associated degradation maintains β cell identity via TGF-β signaling. J Clin Invest 2020; 130(7): 3499-510.
[http://dx.doi.org/10.1172/JCI134874] [PMID: 32182217]
[155]
Kang Y, Ling J, Suzuki R, et al. SMAD4 regulates cell motility through transcription of N-cadherin in human pancreatic ductal epithelium. PLoS One 2014; 9(9): e107948.
[http://dx.doi.org/10.1371/journal.pone.0107948] [PMID: 25264609]
[156]
Rulifson IC, Karnik SK, Heiser PW, et al. Wnt signaling regulates pancreatic beta cell proliferation. Proc Natl Acad Sci USA 2007; 104(15): 6247-52.
[http://dx.doi.org/10.1073/pnas.0701509104] [PMID: 17404238]
[157]
Liu Z, Habener JF. Wnt signaling in pancreatic islets. Adv Exp Med Biol 2010; 654: 391-419.
[http://dx.doi.org/10.1007/978-90-481-3271-3_17] [PMID: 20217507]
[158]
Valenta T, Hausmann G, Basler K. The many faces and functions of β-catenin. EMBO J 2012; 31(12): 2714-36.
[http://dx.doi.org/10.1038/emboj.2012.150] [PMID: 22617422]
[159]
Loh C-Y, Chai JY, Tang TF, et al. The e-cadherin and n-cadherin switch in epithelial-to-mesenchymal transition: Signaling, therapeutic implications, and challenges. Cells 2019; 8(10): 1118.
[http://dx.doi.org/10.3390/cells8101118] [PMID: 31547193]
[160]
Basu S, Cheriyamundath S, Ben-Ze’ev A. Cell-cell adhesion: Linking Wnt/β-catenin signaling with partial EMT and stemness traits in tumorigenesis. F1000Res 2018; 7: F1000 Faculty Rev-1488.
[161]
Ikonomou L, Geras-Raaka E, Raaka BM, Gershengorn MC. Beta-catenin signalling in mesenchymal islet-derived precursor cells. Cell Prolif 2008; 41(3): 474-91.
[http://dx.doi.org/10.1111/j.1365-2184.2008.00527.x] [PMID: 18422699]
[162]
Lenz A, Toren-Haritan G, Efrat S. Redifferentiation of adult human β cells expanded in vitro by inhibition of the WNT pathway. PLoS One 2014; 9(11): e112914.
[http://dx.doi.org/10.1371/journal.pone.0112914] [PMID: 25393025]
[163]
Jazurek-Ciesiolka M, Janikiewicz J, Dobrzyn P, Dziewulska A, Kozinski K, Dobrzyn A. Oleic acid increases the transcriptional activity of FoxO1 by promoting its nuclear translocation and β-catenin binding in pancreatic β-cells. Biochim Biophys Acta Mol Basis Dis 2019; 1865(10): 2753-64.
[http://dx.doi.org/10.1016/j.bbadis.2019.06.018] [PMID: 31255704]
[164]
Bar Y, Russ HA, Knoller S, Ouziel-Yahalom L, Efrat S. HES-1 is involved in adaptation of adult human beta-cells to proliferation in vitro. Diabetes 2008; 57(9): 2413-20.
[http://dx.doi.org/10.2337/db07-1323] [PMID: 18599525]
[165]
Bar Y, Russ HA, Sintov E, Anker-Kitai L, Knoller S, Efrat S. Redifferentiation of expanded human pancreatic β-cell-derived cells by inhibition of the NOTCH pathway. J Biol Chem 2012; 287(21): 17269-80.
[http://dx.doi.org/10.1074/jbc.M111.319152] [PMID: 22457355]
[166]
Voutsadakis IA. Ubiquitination and the Ubiquitin-Proteasome System as regulators of transcription and transcription factors in epithelial mesenchymal transition of cancer. Tumour Biol 2012; 33(4): 897-910.
[http://dx.doi.org/10.1007/s13277-012-0355-x] [PMID: 22399444]
[167]
Díaz VM, Viñas-Castells R, García de Herreros A. Regulation of the protein stability of EMT transcription factors. Cell Adhes Migr 2014; 8(4): 418-28.
[http://dx.doi.org/10.4161/19336918.2014.969998] [PMID: 25482633]
[168]
Banno A, Garcia DA, van Baarsel ED, et al. Downregulation of 26S proteasome catalytic activity promotes epithelial-mesenchymal transition. Oncotarget 2016; 7(16): 21527-41.
[http://dx.doi.org/10.18632/oncotarget.7596] [PMID: 26930717]
[169]
Goldberg AL. Protein degradation and protection against misfolded or damaged proteins. Nature 2003; 426(6968): 895-9.
[http://dx.doi.org/10.1038/nature02263] [PMID: 14685250]
[170]
Le Guerroué F, Youle RJ. Ubiquitin signaling in neurodegenerative diseases: An autophagy and proteasome perspective. Cell Death Differ 2021; 28(2): 439-54.
[http://dx.doi.org/10.1038/s41418-020-00667-x] [PMID: 33208890]
[171]
Sun-Wang JL, Yarritu-Gallego A, Ivanova S, Zorzano A. The ubiquitin-proteasome system and autophagy: Self-digestion for metabolic health. Trends Endocrinol Metab 2021; 32(8): 594-608.
[http://dx.doi.org/10.1016/j.tem.2021.04.015] [PMID: 34034951]
[172]
Lingbeck JM, Trausch-Azar JS, Ciechanover A, Schwartz AL. Determinants of nuclear and cytoplasmic ubiquitin-mediated degradation of MyoD. J Biol Chem 2003; 278(3): 1817-23.
[http://dx.doi.org/10.1074/jbc.M208815200] [PMID: 12397066]
[173]
Nandi D, Tahiliani P, Kumar A, Chandu D. The ubiquitin-proteasome system. J Biosci 2006; 31(1): 137-55.
[http://dx.doi.org/10.1007/BF02705243] [PMID: 16595883]
[174]
Varshavsky A. The early history of the ubiquitin field. Protein Sci 2006; 15(3): 647-54.
[http://dx.doi.org/10.1110/ps.052012306] [PMID: 16501229]
[175]
Ventii KH, Wilkinson KD. Protein partners of deubiquitinating enzymes. Biochem J 2008; 414(2): 161-75.
[http://dx.doi.org/10.1042/BJ20080798] [PMID: 18687060]
[176]
Voutsadakis IA. The ubiquitin-proteasome system and signal transduction pathways regulating epithelial mesenchymal transition of cancer. J Biomed Sci 2012; 19(1): 67.
[http://dx.doi.org/10.1186/1423-0127-19-67] [PMID: 22827778]
[177]
Tsubakihara Y, Moustakas A. Epithelial-mesenchymal transition and metastasis under the control of transforming growth factor β. Int J Mol Sci 2018; 19(11): 3672.
[http://dx.doi.org/10.3390/ijms19113672] [PMID: 30463358]
[178]
Claiborn KC, Sachdeva MM, Cannon CE, Groff DN, Singer JD, Stoffers DA. Pcif1 modulates Pdx1 protein stability and pancreatic β cell function and survival in mice. J Clin Invest 2010; 120(10): 3713-21.
[http://dx.doi.org/10.1172/JCI40440] [PMID: 20811152]
[179]
Sancho R, Gruber R, Gu G, Behrens A. Loss of Fbw7 reprograms adult pancreatic ductal cells into α, δ, and β cells. Cell Stem Cell 2014; 15(2): 139-53.
[http://dx.doi.org/10.1016/j.stem.2014.06.019] [PMID: 25105579]
[180]
Itoh M, Kim C-H, Palardy G, et al. Mind bomb is a ubiquitin ligase that is essential for efficient activation of Notch signaling by Delta. Dev Cell 2003; 4(1): 67-82.
[http://dx.doi.org/10.1016/S1534-5807(02)00409-4] [PMID: 12530964]
[181]
Horn S, Kobberup S, Jørgensen MC, et al. Mind bomb 1 is required for pancreatic β-cell formation. Proc Natl Acad Sci USA 2012; 109(19): 7356-61.
[http://dx.doi.org/10.1073/pnas.1203605109] [PMID: 22529374]
[182]
Han SI, Aramata S, Yasuda K, Kataoka K. MafA stability in pancreatic β cells is regulated by glucose and is dependent on its constitutive phosphorylation at multiple sites by glycogen synthase kinase 3. Mol Cell Biol 2007; 27(19): 6593-605.
[http://dx.doi.org/10.1128/MCB.01573-06] [PMID: 17682063]
[183]
Malenczyk K, Szodorai E, Schnell R, et al. Secretagogin protects Pdx1 from proteasomal degradation to control a transcriptional program required for β cell specification. Mol Metab 2018; 14: 108-20.
[http://dx.doi.org/10.1016/j.molmet.2018.05.019] [PMID: 29910119]
[184]
Kitiphongspattana K, Mathews CE, Leiter EH, Gaskins HR. Proteasome inhibition alters glucose-stimulated (pro)insulin secretion and turnover in pancreatic β-cells. J Biol Chem 2005; 280(16): 15727-34.
[http://dx.doi.org/10.1074/jbc.M410876200] [PMID: 15705591]
[185]
Yan F-F, Lin C-W, Cartier EA, Shyng SL. Role of ubiquitin-proteasome degradation pathway in biogenesis efficiency of β-cell ATP-sensitive potassium channels. Am J Physiol Cell Physiol 2005; 289(5): C1351-9.
[http://dx.doi.org/10.1152/ajpcell.00240.2005] [PMID: 15987767]
[186]
Kawaguchi M, Minami K, Nagashima K, Seino S. Essential role of ubiquitin-proteasome system in normal regulation of insulin secretion. J Biol Chem 2006; 281(19): 13015-20.
[http://dx.doi.org/10.1074/jbc.M601228200] [PMID: 16543239]
[187]
Gorrepati KDD, Lupse B, Annamalai K, Yuan T, Maedler K, Ardestani A. Loss of deubiquitinase USP1 blocks pancreatic β-cell apoptosis by inhibiting DNA damage response. iScience 2018; 1: 72-86.
[http://dx.doi.org/10.1016/j.isci.2018.02.003] [PMID: 30227958]
[188]
Yamagata K, Nammo T, Moriwaki M, et al. Overexpression of dominant-negative mutant hepatocyte nuclear fctor-1 alpha in pancreatic beta-cells causes abnormal islet architecture with decreased expression of E-cadherin, reduced beta-cell proliferation, and diabetes. Diabetes 2002; 51(1): 114-23.
[http://dx.doi.org/10.2337/diabetes.51.1.114] [PMID: 11756330]
[189]
Kim MH, Rebbert ML, Ro H, Won M, Dawid IB. Cell adhesion in zebrafish embryos is modulated by March 8. PLoS One 2014; 9(4): e94873.
[http://dx.doi.org/10.1371/journal.pone.0094873] [PMID: 24752240]
[190]
Zhu J, Deng S, Duan J, et al. FBXL20 acts as an invasion inducer and mediates E-cadherin in colorectal adenocarcinoma. Oncol Lett 2014; 7(6): 2185-91.
[http://dx.doi.org/10.3892/ol.2014.2031] [PMID: 24932313]
[191]
Shrestha H, Ryu T, Seo YW, et al. Hakai, an E3-ligase for E-cadherin, stabilizes δ-catenin through Src kinase. Cell Signal 2017; 31: 135-45.
[http://dx.doi.org/10.1016/j.cellsig.2017.01.009] [PMID: 28069439]
[192]
Niño CA, Sala S, Polo S. When ubiquitin meets E-cadherin: Plasticity of the epithelial cellular barrier. Semin Cell Dev Biol 2019; 93: 136-44.
[http://dx.doi.org/10.1016/j.semcdb.2018.12.005] [PMID: 30566893]
[193]
Tang L, Yi X-M, Chen J, et al. Ubiquitin ligase UBE3C promotes melanoma progression by increasing epithelial-mesenchymal transition in melanoma cells. Oncotarget 2016; 7(13): 15738-46.
[http://dx.doi.org/10.18632/oncotarget.7393] [PMID: 26894856]
[194]
Jeon YK, Kim CK, Hwang KR, et al. Pellino-1 promotes lung carcinogenesis via the stabilization of Slug and Snail through K63-mediated polyubiquitination. Cell Death Differ 2017; 24(3): 469-80.
[http://dx.doi.org/10.1038/cdd.2016.143] [PMID: 28009353]
[195]
Yan L, Lin M, Pan S, Assaraf YG, Wang ZW, Zhu X. Emerging roles of F-box proteins in cancer drug resistance. Drug Resist Updat 2020; 49: 100673.
[http://dx.doi.org/10.1016/j.drup.2019.100673] [PMID: 31877405]
[196]
Shi J, Liu Y, Xu X, et al. Deubiquitinase USP47/UBP64E regulates β-catenin ubiquitination and degradation and plays a positive role in Wnt signaling. Mol Cell Biol 2015; 35(19): 3301-11.
[http://dx.doi.org/10.1128/MCB.00373-15] [PMID: 26169834]
[197]
Cai J, Culley MK, Zhao Y, Zhao J. The role of ubiquitination and deubiquitination in the regulation of cell junctions. Protein Cell 2018; 9(9): 754-69.
[http://dx.doi.org/10.1007/s13238-017-0486-3] [PMID: 29080116]
[198]
Lin Y, Wang Y, Shi Q, et al. Stabilization of the transcription factors slug and twist by the deubiquitinase dub3 is a key requirement for tumor metastasis. Oncotarget 2017; 8(43): 75127-40.
[http://dx.doi.org/10.18632/oncotarget.20561] [PMID: 29088851]
[199]
Filios SR, Xu G, Chen J, Hong K, Jing G, Shalev A. MicroRNA-200 is induced by thioredoxin-interacting protein and regulates Zeb1 pro-tein signaling and beta cell apoptosis. J Biol Chem 2014; 289(52): 36275-83.
[http://dx.doi.org/10.1074/jbc.M114.592360] [PMID: 25391656]
[200]
Joglekar MV, Patil D, Joglekar VM, et al. The miR-30 family microRNAs confer epithelial phenotype to human pancreatic cells. Islets 2009; 1(2): 137-47.
[http://dx.doi.org/10.4161/isl.1.2.9578] [PMID: 21099261]
[201]
Beattie GM, Rubin JS, Mally MI, Otonkoski T, Hayek A. Regulation of proliferation and differentiation of human fetal pancreatic islet cells by extracellular matrix, hepatocyte growth factor, and cell-cell contact. Diabetes 1996; 45(9): 1223-8.
[http://dx.doi.org/10.2337/diab.45.9.1223] [PMID: 8772726]
[202]
Beattie GM, Itkin-Ansari P, Cirulli V, et al. Sustained proliferation of PDX-1+ cells derived from human islets. Diabetes 1999; 48(5): 1013-9.
[http://dx.doi.org/10.2337/diabetes.48.5.1013] [PMID: 10331405]
[203]
Bar-Nur O, Gerli MFM, Di Stefano B, et al. Direct reprogramming of mouse fibroblasts into functional skeletal muscle progenitors. Stem Cell Reports 2018; 10(5): 1505-21.
[http://dx.doi.org/10.1016/j.stemcr.2018.04.009] [PMID: 29742392]
[204]
Sintov E, Nathan G, Knoller S, Pasmanik-Chor M, Russ HA, Efrat S. Inhibition of ZEB1 expression induces redifferentiation of adult human β cells expanded in vitro. Sci Rep 2015; 5(1): 13024.
[http://dx.doi.org/10.1038/srep13024] [PMID: 26264186]

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