Generic placeholder image

Current Cancer Drug Targets

Editor-in-Chief

ISSN (Print): 1568-0096
ISSN (Online): 1873-5576

Mini-Review Article

Emerging Prospects for the Study of Colorectal Cancer Stem Cells using Patient-derived Organoids

Author(s): Ling Ding, Yuning Yang, Qin Lu, Zhiyun Cao* and Nathaniel Weygant*

Volume 22, Issue 3, 2022

Published on: 17 March, 2022

Page: [195 - 208] Pages: 14

DOI: 10.2174/1568009622666220117124546

Price: $65

Abstract

Human colorectal cancer (CRC) patient-derived organoids (PDOs) are a powerful ex vivo platform to directly assess the impact of molecular alterations and therapies on tumor cell proliferation, differentiation, response to chemotherapy, tumor-microenvironment interactions, and other facets of CRC biology. Next-generation sequencing studies have demonstrated that CRC is a highly heterogeneous disease with multiple distinct subtypes. PDOs are a promising new tool to study CRC due to their ability to accurately recapitulate their source tumor and thus reproduce this heterogeneity. This review summarizes the state-of-the-art for CRC PDOs in the study of cancer stem cells (CSCs) and the cancer stem cell niche. Areas of focus include the relevance of PDOs to understanding CSC-related paracrine signaling, identifying interactions between CSCs and the tumor microenvironment, and modeling CSC-driven resistance to chemotherapies and targeted therapies. Finally, we summarize current findings regarding the identification and verification of CSC targets using PDOs and their potential use in personalized medicine.

Keywords: Colorectal cancer, cancer stem cells, tumor microenvironment, patient-derived organoids, personalized medicine, LGR5.

Graphical Abstract

[1]
Sung, H.; Ferlay, J.; Siegel, R.L.; Laversanne, M.; Soerjomataram, I.; Jemal, A.; Bray, F. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin., 2021, 71(3), 209-249.
[http://dx.doi.org/10.3322/caac.21660] [PMID: 33538338]
[2]
Yan, H.H.N.; Siu, H.C.; Ho, S.L.; Yue, S.S.K.; Gao, Y.; Tsui, W.Y.; Chan, D.; Chan, A.S.; Wong, J.W.H.; Man, A.H.Y.; Lee, B.C.H.; Chan, A.S.Y.; Chan, A.K.W.; Hui, H.S.; Cheung, A.K.L.; Law, W.L.; Lo, O.S.H.; Yuen, S.T.; Clevers, H.; Leung, S.Y. Organoid cultures of early-onset colorectal cancers reveal distinct and rare genetic profiles. Gut, 2020, 69(12), 2165-2179.
[http://dx.doi.org/10.1136/gutjnl-2019-320019] [PMID: 32217638]
[3]
Hanahan, D.; Coussens, L.M. Accessories to the crime: Functions of cells recruited to the tumor microenvironment. Cancer Cell, 2012, 21(3), 309-322.
[http://dx.doi.org/10.1016/j.ccr.2012.02.022] [PMID: 22439926]
[4]
Hui, L.; Chen, Y. Tumor microenvironment: Sanctuary of the devil. Cancer Lett., 2015, 368(1), 7-13.
[http://dx.doi.org/10.1016/j.canlet.2015.07.039] [PMID: 26276713]
[5]
Guinney, J.; Dienstmann, R.; Wang, X.; de Reyniès, A.; Schlicker, A.; Soneson, C.; Marisa, L.; Roepman, P.; Nyamundanda, G.; Angelino, P.; Bot, B.M.; Morris, J.S.; Simon, I.M.; Gerster, S.; Fessler, E.; De Sousa E Melo, F.; Missiaglia, E.; Ramay, H.; Barras, D.; Homicsko, K.; Maru, D.; Manyam, G.C.; Broom, B.; Boige, V.; Perez-Villamil, B.; Laderas, T.; Salazar, R.; Gray, J.W.; Hanahan, D.; Tabernero, J.; Bernards, R.; Friend, S.H.; Laurent-Puig, P.; Medema, J.P.; Sadanandam, A.; Wessels, L.; Delorenzi, M.; Kopetz, S.; Vermeulen, L.; Tejpar, S. The consensus molecular subtypes of colorectal cancer. Nat. Med., 2015, 21(11), 1350-1356.
[http://dx.doi.org/10.1038/nm.3967] [PMID: 26457759]
[6]
Dienstmann, R.; Vermeulen, L.; Guinney, J.; Kopetz, S.; Tejpar, S.; Tabernero, J. Consensus molecular subtypes and the evolution of precision medicine in colorectal cancer. Nat. Rev. Cancer, 2017, 17(2), 79-92.
[http://dx.doi.org/10.1038/nrc.2016.126] [PMID: 28050011]
[7]
Vermeulen, L.; De Sousa E Melo, F.; van der Heijden, M.; Cameron, K.; de Jong, J.H.; Borovski, T.; Tuynman, J.B.; Todaro, M.; Merz, C.; Rodermond, H.; Sprick, M.R.; Kemper, K.; Richel, D.J.; Stassi, G.; Medema, J.P. Wnt activity defines colon cancer stem cells and is regulated by the microenvironment. Nat. Cell Biol., 2010, 12(5), 468-476.
[http://dx.doi.org/10.1038/ncb2048] [PMID: 20418870]
[8]
Quail, D.F.; Taylor, M.J.; Postovit, L.M. Microenvironmental regulation of cancer stem cell phenotypes. Curr. Stem Cell Res. Ther., 2012, 7(3), 197-216.
[http://dx.doi.org/10.2174/157488812799859838] [PMID: 22329582]
[9]
Fessler, E.; Dijkgraaf, F.E.; De Sousa E Melo, F.; Medema, J.P. Cancer stem cell dynamics in tumor progression and metastasis: Is the microenvironment to blame? Cancer Lett., 2013, 341(1), 97-104.
[http://dx.doi.org/10.1016/j.canlet.2012.10.015] [PMID: 23089245]
[10]
Oskarsson, T.; Batlle, E.; Massagué, J. Metastatic stem cells: Sources, niches, and vital pathways. Cell Stem Cell, 2014, 14(3), 306-321.
[http://dx.doi.org/10.1016/j.stem.2014.02.002] [PMID: 24607405]
[11]
Plaks, V.; Kong, N.; Werb, Z. The cancer stem cell niche: how essential is the niche in regulating stemness of tumor cells? Cell Stem Cell, 2015, 16(3), 225-238.
[http://dx.doi.org/10.1016/j.stem.2015.02.015] [PMID: 25748930]
[12]
Barker, N.; Ridgway, R.A.; van Es, J.H.; van de Wetering, M.; Begthel, H.; van den Born, M.; Danenberg, E.; Clarke, A.R.; Sansom, O.J.; Clevers, H. Crypt stem cells as the cells-of-origin of intestinal cancer. Nature, 2009, 457(7229), 608-611.
[http://dx.doi.org/10.1038/nature07602] [PMID: 19092804]
[13]
Qi, Z.; Chen, Y.G. Regulation of intestinal stem cell fate specification. Sci. China Life Sci., 2015, 58(6), 570-578.
[http://dx.doi.org/10.1007/s11427-015-4859-7] [PMID: 25951932]
[14]
Merlos-Suárez, A.; Barriga, F.M.; Jung, P.; Iglesias, M.; Céspedes, M.V.; Rossell, D.; Sevillano, M.; Hernando-Momblona, X.; da Silva-Diz, V.; Muñoz, P.; Clevers, H.; Sancho, E.; Mangues, R.; Batlle, E. The intestinal stem cell signature identifies colorectal cancer stem cells and predicts disease relapse. Cell Stem Cell, 2011, 8(5), 511-524.
[http://dx.doi.org/10.1016/j.stem.2011.02.020] [PMID: 21419747]
[15]
Tomasetti, C.; Vogelstein, B. Cancer etiology. Variation in cancer risk among tissues can be explained by the number of stem cell divisions. Science, 2015, 347(6217), 78-81.
[http://dx.doi.org/10.1126/science.1260825] [PMID: 25554788]
[16]
Barker, N.; van Es, J.H.; Kuipers, J.; Kujala, P.; van den Born, M.; Cozijnsen, M.; Haegebarth, A.; Korving, J.; Begthel, H.; Peters, P.J.; Clevers, H. Identification of stem cells in small intestine and colon by marker gene Lgr5. Nature, 2007, 449(7165), 1003-1007.
[http://dx.doi.org/10.1038/nature06196] [PMID: 17934449]
[17]
Metcalfe, C.; Kljavin, N.M.; Ybarra, R.; de Sauvage, F.J. Lgr5+ stem cells are indispensable for radiation-induced intestinal regeneration. Cell Stem Cell, 2014, 14(2), 149-159.
[http://dx.doi.org/10.1016/j.stem.2013.11.008] [PMID: 24332836]
[18]
Yan, K.S.; Chia, L.A.; Li, X.; Ootani, A.; Su, J.; Lee, J.Y.; Su, N.; Luo, Y.; Heilshorn, S.C.; Amieva, M.R.; Sangiorgi, E.; Capecchi, M.R.; Kuo, C.J. The intestinal stem cell markers Bmi1 and Lgr5 identify two functionally distinct populations. Proc. Natl. Acad. Sci. USA, 2012, 109(2), 466-471.
[http://dx.doi.org/10.1073/pnas.1118857109] [PMID: 22190486]
[19]
Tian, H.; Biehs, B.; Warming, S.; Leong, K.G.; Rangell, L.; Klein, O.D.; de Sauvage, F.J. A reserve stem cell population in small intestine renders Lgr5-positive cells dispensable. Nature, 2011, 478(7368), 255-259.
[http://dx.doi.org/10.1038/nature10408] [PMID: 21927002]
[20]
Vermeulen, L.; Snippert, H.J. Stem cell dynamics in homeostasis and cancer of the intestine. Nat. Rev. Cancer, 2014, 14(7), 468-480.
[http://dx.doi.org/10.1038/nrc3744] [PMID: 24920463]
[21]
Muñoz, J.; Stange, D.E.; Schepers, A.G.; van de Wetering, M.; Koo, B.K.; Itzkovitz, S.; Volckmann, R.; Kung, K.S.; Koster, J.; Radulescu, S.; Myant, K.; Versteeg, R.; Sansom, O.J.; van Es, J.H.; Barker, N.; van Oudenaarden, A.; Mohammed, S.; Heck, A.J.; Clevers, H. The Lgr5 intestinal stem cell signature: Robust expression of proposed quiescent '+4′ cell markers. EMBO J., 2012, 31(14), 3079-3091.
[http://dx.doi.org/10.1038/emboj.2012.166] [PMID: 22692129]
[22]
Sato, T.; van Es, J.H.; Snippert, H.J.; Stange, D.E.; Vries, R.G.; van den Born, M.; Barker, N.; Shroyer, N.F.; van de Wetering, M.; Clevers, H. Paneth cells constitute the niche for Lgr5 stem cells in intestinal crypts. Nature, 2011, 469(7330), 415-418.
[http://dx.doi.org/10.1038/nature09637] [PMID: 21113151]
[23]
Jung, P.; Sato, T.; Merlos-Suárez, A.; Barriga, F.M.; Iglesias, M.; Rossell, D.; Auer, H.; Gallardo, M.; Blasco, M.A.; Sancho, E.; Clevers, H.; Batlle, E. Isolation and in vitro expansion of human colonic stem cells. Nat. Med., 2011, 17(10), 1225-1227.
[http://dx.doi.org/10.1038/nm.2470] [PMID: 21892181]
[24]
Schwitalla, S.; Fingerle, A.A.; Cammareri, P.; Nebelsiek, T.; Göktuna, S.I.; Ziegler, P.K.; Canli, O.; Heijmans, J.; Huels, D.J.; Moreaux, G.; Rupec, R.A.; Gerhard, M.; Schmid, R.; Barker, N.; Clevers, H.; Lang, R.; Neumann, J.; Kirchner, T.; Taketo, M.M.; van den Brink, G.R.; Sansom, O.J.; Arkan, M.C.; Greten, F.R. Intestinal tumorigenesis initiated by dedifferentiation and acquisition of stem-cell-like properties. Cell, 2013, 152(1-2), 25-38.
[http://dx.doi.org/10.1016/j.cell.2012.12.012] [PMID: 23273993]
[25]
Todaro, M.; Gaggianesi, M.; Catalano, V.; Benfante, A.; Iovino, F.; Biffoni, M.; Apuzzo, T.; Sperduti, I.; Volpe, S.; Cocorullo, G.; Gulotta, G.; Dieli, F.; De Maria, R.; Stassi, G. CD44v6 is a marker of constitutive and reprogrammed cancer stem cells driving colon cancer metastasis. Cell Stem Cell, 2014, 14(3), 342-356.
[http://dx.doi.org/10.1016/j.stem.2014.01.009] [PMID: 24607406]
[26]
Zeuner, A.; Todaro, M.; Stassi, G.; De Maria, R. Colorectal cancer stem cells: From the crypt to the clinic. Cell Stem Cell, 2014, 15(6), 692-705.
[http://dx.doi.org/10.1016/j.stem.2014.11.012] [PMID: 25479747]
[27]
Marzano, M.; Fosso, B.; Piancone, E.; Defazio, G.; Pesole, G.; De Robertis, M. Stem cell impairment at the host-microbiota interface in colorectal cancer. Cancers (Basel), 2021, 13(5), 996.
[http://dx.doi.org/10.3390/cancers13050996] [PMID: 33673612]
[28]
De Robertis, M.; Poeta, M.L.; Signori, E.; Fazio, V.M. Current understanding and clinical utility of miRNAs regulation of colon cancer stem cells. Semin. Cancer Biol., 2018, 53, 232-247.
[http://dx.doi.org/10.1016/j.semcancer.2018.08.008] [PMID: 30130662]
[29]
Hatano, Y.; Fukuda, S.; Hisamatsu, K.; Hirata, A.; Hara, A.; Tomita, H. Multifaceted interpretation of colon cancer stem cells. Int. J. Mol. Sci., 2017, 18(7), E1446.
[http://dx.doi.org/10.3390/ijms18071446] [PMID: 28678194]
[30]
Du, L.; Cheng, Q.; Zheng, H.; Liu, J.; Liu, L.; Chen, Q. Targeting stemness of cancer stem cells to fight colorectal cancers. Semin. Cancer Biol., 2021, S1044-579X(21), 00041-9.
[http://dx.doi.org/10.1016/j.semcancer.2021.02.012] [PMID: 33631296]
[31]
Sato, T.; Vries, R.G.; Snippert, H.J.; van de Wetering, M.; Barker, N.; Stange, D.E.; van Es, J.H.; Abo, A.; Kujala, P.; Peters, P.J.; Clevers, H. Single Lgr5 stem cells build crypt-villus structures in vitro without a mesenchymal niche. Nature, 2009, 459(7244), 262-265.
[http://dx.doi.org/10.1038/nature07935] [PMID: 19329995]
[32]
Pinto, D.; Gregorieff, A.; Begthel, H.; Clevers, H. Canonical Wnt signals are essential for homeostasis of the intestinal epithelium. Genes Dev., 2003, 17(14), 1709-1713.
[http://dx.doi.org/10.1101/gad.267103] [PMID: 12865297]
[33]
Kim, K.A.; Kakitani, M.; Zhao, J.; Oshima, T.; Tang, T.; Binnerts, M.; Liu, Y.; Boyle, B.; Park, E.; Emtage, P.; Funk, W.D.; Tomizuka, K. Mitogenic influence of human R-spondin1 on the intestinal epithelium. Science, 2005, 309(5738), 1256-1259.
[http://dx.doi.org/10.1126/science.1112521] [PMID: 16109882]
[34]
Haramis, A.P.; Begthel, H.; van den Born, M.; van Es, J.; Jonkheer, S.; Offerhaus, G.J.; Clevers, H. De novo crypt formation and juvenile polyposis on BMP inhibition in mouse intestine. Science, 2004, 303(5664), 1684-1686.
[http://dx.doi.org/10.1126/science.1093587] [PMID: 15017003]
[35]
Spence, J.R.; Mayhew, C.N.; Rankin, S.A.; Kuhar, M.F.; Vallance, J.E.; Tolle, K.; Hoskins, E.E.; Kalinichenko, V.V.; Wells, S.I.; Zorn, A.M.; Shroyer, N.F.; Wells, J.M. Directed differentiation of human pluripotent stem cells into intestinal tissue in vitro. Nature, 2011, 470(7332), 105-109.
[http://dx.doi.org/10.1038/nature09691] [PMID: 21151107]
[36]
Sato, T.; Stange, D.E.; Ferrante, M.; Vries, R.G.; Van Es, J.H.; Van den Brink, S.; Van Houdt, W.J.; Pronk, A.; Van Gorp, J.; Siersema, P.D.; Clevers, H. Long-term expansion of epithelial organoids from human colon, adenoma, adenocarcinoma, and Barrett’s epithelium. Gastroenterology, 2011, 141(5), 1762-1772.
[http://dx.doi.org/10.1053/j.gastro.2011.07.050] [PMID: 21889923]
[37]
Tuveson, D.; Clevers, H. Cancer modeling meets human organoid technology. Science, 2019, 364(6444), 952-955.
[http://dx.doi.org/10.1126/science.aaw6985] [PMID: 31171691]
[38]
Linnekamp, J.F.; Hooff, S.R.V.; Prasetyanti, P.R.; Kandimalla, R.; Buikhuisen, J.Y.; Fessler, E.; Ramesh, P.; Lee, K.A.S.T.; Bochove, G.G.W.; de Jong, J.H.; Cameron, K.; Leersum, R.V.; Rodermond, H.M.; Franitza, M.; Nürnberg, P.; Mangiapane, L.R.; Wang, X.; Clevers, H.; Vermeulen, L.; Stassi, G.; Medema, J.P. Consensus molecular subtypes of colorectal cancer are recapitulated in in vitro and in vivo models. Cell Death Differ., 2018, 25(3), 616-633.
[http://dx.doi.org/10.1038/s41418-017-0011-5] [PMID: 29305587]
[39]
Stastna, M.; Janeckova, L.; Hrckulak, D.; Kriz, V.; Korinek, V. Human colorectal cancer from the perspective of mouse models. Genes (Basel), 2019, 10(10), E788.
[http://dx.doi.org/10.3390/genes10100788] [PMID: 31614493]
[40]
Matano, M.; Date, S.; Shimokawa, M.; Takano, A.; Fujii, M.; Ohta, Y.; Watanabe, T.; Kanai, T.; Sato, T. Modeling colorectal cancer using CRISPR-Cas9-mediated engineering of human intestinal organoids. Nat. Med., 2015, 21(3), 256-262.
[http://dx.doi.org/10.1038/nm.3802] [PMID: 25706875]
[41]
Liu, Y.; Chen, Y.G. 2D- and 3D-based intestinal stem cell cultures for personalized medicine. Cells, 2018, 7(12), E225.
[http://dx.doi.org/10.3390/cells7120225] [PMID: 30469504]
[42]
Xie, B.Y.; Wu, A.W. Organoid culture of isolated cells from patient-derived tissues with colorectal cancer. Chin. Med. J. (Engl.), 2016, 129(20), 2469-2475.
[http://dx.doi.org/10.4103/0366-6999.191782] [PMID: 27748340]
[43]
Petrova, T.V.; Nykänen, A.; Norrmén, C.; Ivanov, K.I.; Andersson, L.C.; Haglund, C.; Puolakkainen, P.; Wempe, F.; von Melchner, H.; Gradwohl, G.; Vanharanta, S.; Aaltonen, L.A.; Saharinen, J.; Gentile, M.; Clarke, A.; Taipale, J.; Oliver, G.; Alitalo, K. Transcription factor PROX1 induces colon cancer progression by promoting the transition from benign to highly dysplastic phenotype. Cancer Cell, 2008, 13(5), 407-419.
[http://dx.doi.org/10.1016/j.ccr.2008.02.020] [PMID: 18455124]
[44]
Wiener, Z.; Högström, J.; Hyvönen, V.; Band, A.M.; Kallio, P.; Holopainen, T.; Dufva, O.; Haglund, C.; Kruuna, O.; Oliver, G.; Ben-Neriah, Y.; Alitalo, K. Prox1 promotes expansion of the colorectal cancer stem cell population to fuel tumor growth and ischemia resistance. Cell Rep., 2014, 8(6), 1943-1956.
[http://dx.doi.org/10.1016/j.celrep.2014.08.034] [PMID: 25242330]
[45]
Shiokawa, D.; Sakai, H.; Ohata, H.; Miyazaki, T.; Kanda, Y.; Sekine, S.; Narushima, D.; Hosokawa, M.; Kato, M.; Suzuki, Y.; Takeyama, H.; Kambara, H.; Nakagama, H.; Okamoto, K. Slow- cycling cancer stem cells regulate progression and chemoresistance in colon cancer. Cancer Res., 2020, 80(20), 4451-4464.
[http://dx.doi.org/10.1158/0008-5472.CAN-20-0378] [PMID: 32816913]
[46]
Kozar, S.; Morrissey, E.; Nicholson, A.M.; van der Heijden, M.; Zecchini, H.I.; Kemp, R.; Tavaré, S.; Vermeulen, L.; Winton, D.J. Continuous clonal labeling reveals small numbers of functional stem cells in intestinal crypts and adenomas. Cell Stem Cell, 2013, 13(5), 626-633.
[http://dx.doi.org/10.1016/j.stem.2013.08.001] [PMID: 24035355]
[47]
Cortina, C.; Turon, G.; Stork, D.; Hernando-Momblona, X.; Sevillano, M.; Aguilera, M.; Tosi, S.; Merlos-Suárez, A.; Stephan-Otto Attolini, C.; Sancho, E.; Batlle, E. A genome editing approach to study cancer stem cells in human tumors. EMBO Mol. Med., 2017, 9(7), 869-879.
[http://dx.doi.org/10.15252/emmm.201707550] [PMID: 28468934]
[48]
Ganesh, K.; Basnet, H.; Kaygusuz, Y.; Laughney, A.M.; He, L.; Sharma, R.; O’Rourke, K.P.; Reuter, V.P.; Huang, Y.H.; Turkekul, M.; Emrah, E.; Masilionis, I.; Manova-Todorova, K.; Weiser, M.R.; Saltz, L.B.; Garcia-Aguilar, J.; Koche, R.; Lowe, S.W.; Pe’er, D.; Shia, J.; Massagué, J. L1CAM defines the regenerative origin of metastasis-initiating cells in colorectal cancer. Nat. Can., 2020, 1(1), 28-45.
[http://dx.doi.org/10.1038/s43018-019-0006-x] [PMID: 32656539]
[49]
Dieter, S.M.; Ball, C.R.; Hoffmann, C.M.; Nowrouzi, A.; Herbst, F.; Zavidij, O.; Abel, U.; Arens, A.; Weichert, W.; Brand, K.; Koch, M.; Weitz, J.; Schmidt, M.; von Kalle, C.; Glimm, H. Distinct types of tumor-initiating cells form human colon cancer tumors and metastases. Cell Stem Cell, 2011, 9(4), 357-365.
[http://dx.doi.org/10.1016/j.stem.2011.08.010] [PMID: 21982235]
[50]
Kreso, A.; O’Brien, C.A.; van Galen, P.; Gan, O.I.; Notta, F.; Brown, A.M.; Ng, K.; Ma, J.; Wienholds, E.; Dunant, C.; Pollett, A.; Gallinger, S.; McPherson, J.; Mullighan, C.G.; Shibata, D.; Dick, J.E. Variable clonal repopulation dynamics influence chemotherapy response in colorectal cancer. Science, 2013, 339(6119), 543-548.
[http://dx.doi.org/10.1126/science.1227670] [PMID: 23239622]
[51]
Fujii, M.; Shimokawa, M.; Date, S.; Takano, A.; Matano, M.; Nanki, K.; Ohta, Y.; Toshimitsu, K.; Nakazato, Y.; Kawasaki, K.; Uraoka, T.; Watanabe, T.; Kanai, T.; Sato, T. A colorectal tumor organoid library demonstrates progressive loss of niche factor requirements during tumorigenesis. Cell Stem Cell, 2016, 18(6), 827-838.
[http://dx.doi.org/10.1016/j.stem.2016.04.003] [PMID: 27212702]
[52]
Fumagalli, A.; Oost, K.C.; Kester, L.; Morgner, J.; Bornes, L.; Bruens, L.; Spaargaren, L.; Azkanaz, M.; Schelfhorst, T.; Beerling, E.; Heinz, M.C.; Postrach, D.; Seinstra, D.; Sieuwerts, A.M.; Martens, J.W.M.; van der Elst, S.; van Baalen, M.; Bhowmick, D.; Vrisekoop, N.; Ellenbroek, S.I.J.; Suijkerbuijk, S.J.E.; Snippert, H.J.; van Rheenen, J. Plasticity of Lgr5-negative cancer cells drives metastasis in colorectal cancer. Cell Stem Cell, 2020, 26(4), 569-578.e7.
[http://dx.doi.org/10.1016/j.stem.2020.02.008] [PMID: 32169167]
[53]
Shimokawa, M.; Ohta, Y.; Nishikori, S.; Matano, M.; Takano, A.; Fujii, M.; Date, S.; Sugimoto, S.; Kanai, T.; Sato, T. Visualization and targeting of LGR5+ human colon cancer stem cells. Nature, 2017, 545(7653), 187-192.
[http://dx.doi.org/10.1038/nature22081] [PMID: 28355176]
[54]
Basak, O.; Beumer, J.; Wiebrands, K.; Seno, H.; van Oudenaarden, A.; Clevers, H. Induced quiescence of lgr5+ stem cells in intestinal organoids enables differentiation of hormone-producing enteroendocrine cells. Cell Stem Cell, 2017, 20(2), 177-190.e4.
[http://dx.doi.org/10.1016/j.stem.2016.11.001] [PMID: 27939219]
[55]
de Sousa e Melo, F.; Kurtova, A.V.; Harnoss, J.M.; Kljavin, N.; Hoeck, J.D.; Hung, J.; Anderson, J.E.; Storm, E.E.; Modrusan, Z.; Koeppen, H.; Dijkgraaf, G.J.; Piskol, R.; de Sauvage, F.J. A distinct role for Lgr5+ stem cells in primary and metastatic colon cancer. Nature, 2017, 543(7647), 676-680.
[http://dx.doi.org/10.1038/nature21713] [PMID: 28358093]
[56]
Nakanishi, Y.; Seno, H.; Fukuoka, A.; Ueo, T.; Yamaga, Y.; Maruno, T.; Nakanishi, N.; Kanda, K.; Komekado, H.; Kawada, M.; Isomura, A.; Kawada, K.; Sakai, Y.; Yanagita, M.; Kageyama, R.; Kawaguchi, Y.; Taketo, M.M.; Yonehara, S.; Chiba, T. Dclk1 distinguishes between tumor and normal stem cells in the intestine. Nat. Genet., 2013, 45(1), 98-103.
[http://dx.doi.org/10.1038/ng.2481] [PMID: 23202126]
[57]
Westphalen, C.B.; Asfaha, S.; Hayakawa, Y.; Takemoto, Y.; Lukin, D.J.; Nuber, A.H.; Brandtner, A.; Setlik, W.; Remotti, H.; Muley, A.; Chen, X.; May, R.; Houchen, C.W.; Fox, J.G.; Gershon, M.D.; Quante, M.; Wang, T.C. Long-lived intestinal tuft cells serve as colon cancer-initiating cells. J. Clin. Invest., 2014, 124(3), 1283-1295.
[http://dx.doi.org/10.1172/JCI73434] [PMID: 24487592]
[58]
Sakaguchi, M.; Hisamori, S.; Oshima, N.; Sato, F.; Shimono, Y.; Sakai, Y. miR-137 regulates the tumorigenicity of colon cancer stem cells through the inhibition of DCLK1. MCR, 2016, 14(4), 354-362.
[http://dx.doi.org/10.1158/1541-7786.MCR-15-0380] [PMID: 26747706]
[59]
Goto, N.; Fukuda, A.; Yamaga, Y.; Yoshikawa, T.; Maruno, T.; Maekawa, H.; Inamoto, S.; Kawada, K.; Sakai, Y.; Miyoshi, H.; Taketo, M.M.; Chiba, T.; Seno, H. Lineage tracing and targeting of IL17RB+ tuft cell-like human colorectal cancer stem cells. Proc. Natl. Acad. Sci. USA, 2019, 116(26), 12996-13005.
[http://dx.doi.org/10.1073/pnas.1900251116] [PMID: 31182574]
[60]
Moon, B.S.; Jeong, W.J.; Park, J.; Kim, T.I.; Min, S.; Choi, K.Y. Role of oncogenic K-Ras in cancer stem cell activation by aberrant Wnt/β-catenin signaling. J. Natl. Cancer Inst., 2014, 106(2), djt373.
[http://dx.doi.org/10.1093/jnci/djt373] [PMID: 24491301]
[61]
Peñarando, J.; López-Sánchez, L.M.; Mena, R.; Guil-Luna, S.; Conde, F.; Hernández, V.; Toledano, M.; Gudiño, V.; Raponi, M.; Billard, C.; Villar, C.; Díaz, C.; Gómez-Barbadillo, J.; De la Haba-Rodríguez, J.; Myant, K.; Aranda, E.; Rodríguez-Ariza, A. A role for endothelial nitric oxide synthase in intestinal stem cell proliferation and mesenchymal colorectal cancer. BMC Biol., 2018, 16(1), 3.
[http://dx.doi.org/10.1186/s12915-017-0472-5] [PMID: 29329541]
[62]
Cho, Y.H.; Ro, E.J.; Yoon, J.S.; Mizutani, T.; Kang, D.W.; Park, J.C.; Il Kim, T.; Clevers, H.; Choi, K.Y. 5-FU promotes stemness of colorectal cancer via p53-mediated WNT/β-catenin pathway activation. Nat. Commun., 2020, 11(1), 5321.
[http://dx.doi.org/10.1038/s41467-020-19173-2] [PMID: 33087710]
[63]
van de Wetering, M.; Francies, H.E.; Francis, J.M.; Bounova, G.; Iorio, F.; Pronk, A.; van Houdt, W.; van Gorp, J.; Taylor-Weiner, A.; Kester, L.; McLaren-Douglas, A.; Blokker, J.; Jaksani, S.; Bartfeld, S.; Volckman, R.; van Sluis, P.; Li, V.S.; Seepo, S.; Sekhar Pedamallu, C.; Cibulskis, K.; Carter, S.L.; McKenna, A.; Lawrence, M.S.; Lichtenstein, L.; Stewart, C.; Koster, J.; Versteeg, R.; van Oudenaarden, A.; Saez-Rodriguez, J.; Vries, R.G.; Getz, G.; Wessels, L.; Stratton, M.R.; McDermott, U.; Meyerson, M.; Garnett, M.J.; Clevers, H. Prospective derivation of a living organoid biobank of colorectal cancer patients. Cell, 2015, 161(4), 933-945.
[http://dx.doi.org/10.1016/j.cell.2015.03.053] [PMID: 25957691]
[64]
Lam, M.; Roszik, J.; Kanikarla-Marie, P.; Davis, J.S.; Morris, J.; Kopetz, S.; Menter, D.G. The potential role of platelets in the consensus molecular subtypes of colorectal cancer. Cancer Metastasis Rev., 2017, 36(2), 273-288.
[http://dx.doi.org/10.1007/s10555-017-9678-9] [PMID: 28681242]
[65]
Asano, T.K.; McLeod, R.S. Non steroidal anti-inflammatory drugs (NSAID) and Aspirin for preventing colorectal adenomas and carcinomas. Cochrane Database Syst. Rev., 2004, CD004079(2), CD004079.
[http://dx.doi.org/10.1002/14651858.CD004079.pub2] [PMID: 15106236]
[66]
Dunbar, K.; Valanciute, A.; Lima, A.C.S.; Vinuela, P.F.; Jamieson, T.; Rajasekaran, V.; Blackmur, J.; Ochocka-Fox, A.M.; Guazzelli, A.; Cammareri, P.; Arends, M.J.; Sansom, O.J.; Myant, K.B.; Farrington, S.M.; Dunlop, M.G.; Din, F.V.N. Aspirin rescues WNT-driven stem-like phenotype in human intestinal organoids and increases the WNT antagonist dickkopf-1. Cell. Mol. Gastroenterol. Hepatol., 2021, 11(2), 465-489.
[http://dx.doi.org/10.1016/j.jcmgh.2020.09.010] [PMID: 32971322]
[67]
Verissimo, C.S.; Overmeer, R.M.; Ponsioen, B.; Drost, J.; Mertens, S.; Verlaan-Klink, I.; Gerwen, B.V.; van der Ven, M.; Wetering, M.V.; Egan, D.A.; Bernards, R.; Clevers, H.; Bos, J.L.; Snippert, H.J. Targeting mutant RAS in patient-derived colorectal cancer organoids by combinatorial drug screening. eLife, 2016, 5, e18489.
[http://dx.doi.org/10.7554/eLife.18489] [PMID: 27845624]
[68]
Zhan, T.; Ambrosi, G.; Wandmacher, A.M.; Rauscher, B.; Betge, J.; Rindtorff, N.; Häussler, R.S.; Hinsenkamp, I.; Bamberg, L.; Hessling, B.; Müller-Decker, K.; Erdmann, G.; Burgermeister, E.; Ebert, M.P.; Boutros, M. MEK inhibitors activate wnt signalling and induce stem cell plasticity in colorectal cancer. Nat. Commun., 2019, 10(1), 2197.
[http://dx.doi.org/10.1038/s41467-019-09898-0] [PMID: 31097693]
[69]
Wong, C.C.; Xu, J.; Bian, X.; Wu, J.L.; Kang, W.; Qian, Y.; Li, W.; Chen, H.; Gou, H.; Liu, D.; Yat Luk, S.T.; Zhou, Q.; Ji, F.; Chan, L.S.; Shirasawa, S.; Sung, J.J.; Yu, J. In colorectal cancer cells with mutant KRAS, slc25a22-mediated glutaminolysis reduces DNA demethylation to increase WNT signaling, stemness, and drug resistance. Gastroenterology, 2020, 159(6), 2163-2180.e6.
[http://dx.doi.org/10.1053/j.gastro.2020.08.016] [PMID: 32814111]
[70]
Taipale, J.; Beachy, P.A. The hedgehog and WNT signalling pathways in cancer. Nature, 2001, 411(6835), 349-354.
[http://dx.doi.org/10.1038/35077219] [PMID: 11357142]
[71]
Regan, J.L.; Schumacher, D.; Staudte, S.; Steffen, A.; Haybaeck, J.; Keilholz, U.; Schweiger, C.; Golob-Schwarzl, N.; Mumberg, D.; Henderson, D.; Lehrach, H.; Regenbrecht, C.R.A.; Schäfer, R.; Lange, M. Non-canonical hedgehog signaling is a positive regulator of the WNT pathway and is required for the survival of colon cancer stem cells. Cell Rep., 2017, 21(10), 2813-2828.
[http://dx.doi.org/10.1016/j.celrep.2017.11.025] [PMID: 29212028]
[72]
Barry, E.R.; Morikawa, T.; Butler, B.L.; Shrestha, K.; de la Rosa, R.; Yan, K.S.; Fuchs, C.S.; Magness, S.T.; Smits, R.; Ogino, S.; Kuo, C.J.; Camargo, F.D. Restriction of intestinal stem cell expansion and the regenerative response by YAP. Nature, 2013, 493(7430), 106-110.
[http://dx.doi.org/10.1038/nature11693] [PMID: 23178811]
[73]
Gregorieff, A.; Liu, Y.; Inanlou, M.R.; Khomchuk, Y.; Wrana, J.L. Yap-dependent reprogramming of Lgr5(+) stem cells drives intestinal regeneration and cancer. Nature, 2015, 526(7575), 715-718.
[http://dx.doi.org/10.1038/nature15382] [PMID: 26503053]
[74]
Hong, A.W.; Meng, Z.; Guan, K.L. The Hippo pathway in intestinal regeneration and disease. Nat. Rev. Gastroenterol. Hepatol., 2016, 13(6), 324-337.
[http://dx.doi.org/10.1038/nrgastro.2016.59] [PMID: 27147489]
[75]
Cai, J.; Maitra, A.; Anders, R.A.; Taketo, M.M.; Pan, D. β- Catenin destruction complex-independent regulation of Hippo-YAP signaling by APC in intestinal tumorigenesis. Genes Dev., 2015, 29(14), 1493-1506.
[http://dx.doi.org/10.1101/gad.264515.115] [PMID: 26193883]
[76]
Bisso, A.; Filipuzzi, M.; Gamarra Figueroa, G.P.; Brumana, G.; Biagioni, F.; Doni, M.; Ceccotti, G.; Tanaskovic, N.; Morelli, M.J.; Pendino, V.; Chiacchiera, F.; Pasini, D.; Olivero, D.; Campaner, S.; Sabò, A.; Amati, B. Cooperation between MYC and β-Catenin in liver tumorigenesis requires Yap/Taz. Hepatology, 2020, 72(4), 1430-1443.
[http://dx.doi.org/10.1002/hep.31120] [PMID: 31965581]
[77]
Luo, C.; Balsa, E.; Perry, E.A.; Liang, J.; Tavares, C.D.; Vazquez, F.; Widlund, H.R.; Puigserver, P. H3K27me3-mediated PGC1α gene silencing promotes melanoma invasion through WNT5A and YAP. J. Clin. Invest., 2020, 130(2), 853-862.
[http://dx.doi.org/10.1172/JCI130038] [PMID: 31929186]
[78]
Murakami, S.; Nemazanyy, I.; White, S.M.; Chen, H.; Nguyen, C.D.K.; Graham, G.T.; Saur, D.; Pende, M.; Yi, C. A Yap-Myc- Sox2-p53 regulatory network dictates metabolic homeostasis and differentiation in KRAS-driven pancreatic ductal adenocarcinomas. Dev. Cell, 2019, 51(1), 113-128.e9.
[http://dx.doi.org/10.1016/j.devcel.2019.07.022] [PMID: 31447265]
[79]
Cheung, P.; Xiol, J.; Dill, M.T.; Yuan, W.C.; Panero, R.; Roper, J.; Osorio, F.G.; Maglic, D.; Li, Q.; Gurung, B.; Calogero, R.A.; Yilmaz, Ö.H.; Mao, J.; Camargo, F.D. Regenerative reprogramming of the intestinal stem cell state via hippo signaling suppresses metastatic colorectal cancer. Cell Stem Cell, 2020, 27(4), 590-604.e9.
[http://dx.doi.org/10.1016/j.stem.2020.07.003] [PMID: 32730753]
[80]
Otte, J.; Dizdar, L.; Behrens, B.; Goering, W.; Knoefel, W.T.; Wruck, W.; Stoecklein, N.H.; Adjaye, J. FGF signalling in the self-renewal of colon cancer organoids. Sci. Rep., 2019, 9(1), 17365.
[http://dx.doi.org/10.1038/s41598-019-53907-7] [PMID: 31758153]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy