Login Register Cart 0
Review Article

PCSK9 作为癌症新型选手：新机遇还是无关紧要？

卷 29, 期 6, 2022

发表于: 14 January, 2022

页: [960 - 969] 页: 10

弟呕挨: 10.2174/0929867328666211115122324

价格: $65

conference banner
摘要

最初被描述为参与肝再生和神经元分化的因子，前蛋白转化酶枯草杆菌蛋白酶/kexin 9 型 (PCSK9) 已成为低密度脂蛋白胆固醇的关键调节因子之一。除此之外，许多研究表明 PCSK9 可能在癌症生物学中发挥作用。对于肠胃癌（胃癌和肝癌）和肺癌尤其如此，其中较高的 PCSK9 水平与肿瘤发展和转移的能力增加以及总体存活率降低有关。因此，最近显示阻断 PCSK9 的单克隆抗体与不同类型癌症的免疫疗法协同作用，通过增加细胞毒性 T 细胞的肿瘤内浸润来实现肿瘤生长抑制。抗 PCSK9 疫苗已在动物模型中进行了测试，仅在结肠癌中取得了令人鼓舞的结果。由于这些证据大部分是基于临床前研究，这导致了一些争议和不一致，因此表明需要进一步的研究来澄清这个话题。最后，通过沉默 RNA (siRNA) 调节细胞内 PCSK9 水平可能有助于了解 PCSK9 的生理和病理机制。

关键词: PCSK9、癌症、胆固醇、免疫疗法、疫苗、疗法

« Previous Next »
[1]
Seidah, N.G.; Benjannet, S.; Wickham, L.; Marcinkiewicz, J.; Jasmin, S.B.; Stifani, S.; Basak, A.; Prat, A.; Chretien, M. The secretory proprotein convertase neural apoptosis-regulated convertase 1 (NARC-1): Liver regeneration and neuronal differentiation. Proc. Natl. Acad. Sci. USA, 2003, 100(3), 928-933.
[http://dx.doi.org/10.1073/pnas.0335507100] [PMID: 12552133]
[2]
Leigh, S.E.; Leren, T.P.; Humphries, S.E. Commentary PCSK9 variants: a new database. Atherosclerosis, 2009, 203(1), 32-33.
[http://dx.doi.org/10.1016/j.atherosclerosis.2009.02.006] [PMID: 19249440]
[3]
Mousavi, S.A.; Berge, K.E.; Leren, T.P. The unique role of proprotein convertase subtilisin/kexin 9 in cholesterol homeostasis. J. Intern. Med., 2009, 266(6), 507-519.
[http://dx.doi.org/10.1111/j.1365-2796.2009.02167.x] [PMID: 19930098]
[4]
Sabatine, M.S.; Giugliano, R.P.; Keech, A.C.; Honarpour, N.; Wiviott, S.D.; Murphy, S.A.; Kuder, J.F.; Wang, H.; Liu, T.; Wasserman, S.M.; Sever, P.S.; Pedersen, T.R. Evolocumab and clinical outcomes in patients with cardiovascular disease. N. Engl. J. Med., 2017, 376(18), 1713-1722.
[http://dx.doi.org/10.1056/NEJMoa1615664] [PMID: 28304224]
[5]
Schwartz, G.G.; Steg, P.G.; Szarek, M.; Bhatt, D.L.; Bittner, V.A.; Diaz, R.; Edelberg, J.M.; Goodman, S.G.; Hanotin, C.; Harrington, R.A.; Jukema, J.W.; Lecorps, G.; Mahaffey, K.W.; Moryusef, A.; Pordy, R.; Quintero, K.; Roe, M.T.; Sasiela, W.J.; Tamby, J.F.; Tricoci, P.; White, H.D.; Zeiher, A.M. Alirocumab and cardiovascular outcomes after acute coronary syndrome. N. Engl. J. Med., 2018, 379(22), 2097-2107.
[http://dx.doi.org/10.1056/NEJMoa1801174] [PMID: 30403574]
[6]
Liberale, L.; Montecucco, F.; Camici, G.G.; Dallegri, F.; Vecchie, A.; Carbone, F.; Bonaventura, A. Treatment with Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) inhibitors to reduce cardiovascular inflammation and outcomes. Curr. Med. Chem., 2017, 24(14), 1403-1416.
[http://dx.doi.org/10.2174/0929867324666170303123734] [PMID: 28260498]
[7]
Ruscica, M.; Ferri, N.; Santos, R.D.; Sirtori, C.R.; Corsini, A. Lipid lowering drugs: present status and future developments. Curr. Atheroscler. Rep., 2021, 23(5), 17.
[http://dx.doi.org/10.1007/s11883-021-00918-3] [PMID: 33694108]
[8]
Smeekens, S.P.; Steiner, D.F. Identification of a human insulinoma cDNA encoding a novel mammalian protein structurally related to the yeast dibasic processing protease Kex2. J. Biol. Chem., 1990, 265(6), 2997-3000.
[http://dx.doi.org/10.1016/S0021-9258(19)39721-2] [PMID: 2154467]
[9]
Mbikay, M.; Sirois, F.; Yao, J.; Seidah, N.G.; Chrétien, M. Comparative analysis of expression of the proprotein convertases furin, PACE4, PC1 and PC2 in human lung tumours. Br. J. Cancer, 1997, 75(10), 1509-1514.
[http://dx.doi.org/10.1038/bjc.1997.258] [PMID: 9166946]
[10]
Bassi, D.E.; Fu, J.; Lopez de Cicco, R.; Klein-Szanto, A.J. Proprotein convertases: “Master switches” in the regulation of tumor growth and progression. Mol. Carcinog., 2005, 44(3), 151-161.
[http://dx.doi.org/10.1002/mc.20134] [PMID: 16167351]
[11]
Mahboobnia, K.; Pirro, M.; Marini, E.; Grignani, F.; Bezsonov, E.E.; Jamialahmadi, T.; Sahebkar, A. PCSK9 and cancer: Rethinking the link. Biomed. Pharmacother., 2021, 140, 111758.
[http://dx.doi.org/10.1016/j.biopha.2021.111758] [PMID: 34058443]
[12]
Bhattacharya, A.; Chowdhury, A.; Chaudhury, K.; Shukla, P.C. Proprotein convertase subtilisin/kexin type 9 (PCSK9): A potential multifaceted player in cancer. Biochim. Biophys. Acta Rev. Cancer, 2021, 1876(1), 188581.
[http://dx.doi.org/10.1016/j.bbcan.2021.188581] [PMID: 34144130]
[13]
Spolitu, S.; Dai, W.; Zadroga, J.A.; Ozcan, L. Proprotein convertase subtilisin/kexin type 9 and lipid metabolism. Curr. Opin. Lipidol., 2019, 30(3), 186-191.
[http://dx.doi.org/10.1097/MOL.0000000000000601] [PMID: 30925519]
[14]
Horton, J.D.; Cohen, J.C.; Hobbs, H.H. Molecular biology of PCSK9: its role in LDL metabolism. Trends Biochem. Sci., 2007, 32(2), 71-77.
[http://dx.doi.org/10.1016/j.tibs.2006.12.008] [PMID: 17215125]
[15]
Sun, H.; Krauss, R.M.; Chang, J.T.; Teng, B.B. PCSK9 deficiency reduces atherosclerosis, apolipoprotein B secretion, and endothelial dysfunction. J. Lipid Res., 2018, 59(2), 207-223.
[http://dx.doi.org/10.1194/jlr.M078360] [PMID: 29180444]
[16]
Paciullo, F.; Momi, S.; Gresele, P. PCSK9 in haemostasis and thrombosis: Possible pleiotropic effects of PCSK9 inhibitors in cardiovascular prevention. Thromb. Haemost., 2019, 119(3), 359-367.
[http://dx.doi.org/10.1055/s-0038-1676863] [PMID: 30605918]
[17]
Macchi, C.; Ferri, N.; Sirtori, C.R.; Corsini, A.; Banach, M.; Ruscica, M. Proprotein convertase subtilisin/kexin type 9: a view beyond the canonical cholesterol-lowering impact. Am. J. Pathol., 2021, 191(8), 1385-1397.
[http://dx.doi.org/10.1016/j.ajpath.2021.04.016] [PMID: 34019847]
[18]
Ding, Z.; Pothineni, N.V.K.; Goel, A.; Lüscher, T.F.; Mehta, J.L. PCSK9 and inflammation: Role of shear stress, pro-inflammatory cytokines, and LOX-1. Cardiovasc. Res., 2020, 116(5), 908-915.
[http://dx.doi.org/10.1093/cvr/cvz313] [PMID: 31746997]
[19]
Boyd, J.H.; Fjell, C.D.; Russell, J.A.; Sirounis, D.; Cirstea, M.S.; Walley, K.R. Increased plasma PCSK9 levels are associated with reduced endotoxin clearance and the development of acute organ failures during sepsis. J. Innate Immun., 2016, 8(2), 211-220.
[http://dx.doi.org/10.1159/000442976] [PMID: 26756586]
[20]
Genga, K.R.; Lo, C.; Cirstea, M.S.; Leitao Filho, F.S.; Walley, K.R.; Russell, J.A.; Linder, A.; Francis, G.A.; Boyd, J.H. Impact of PCSK9 loss-of-function genotype on 1-year mortality and recurrent infection in sepsis survivors. EBioMedicine, 2018, 38, 257-264.
[http://dx.doi.org/10.1016/j.ebiom.2018.11.032] [PMID: 30473376]
[21]
Rannikko, J.; Jacome Sanz, D.; Ortutay, Z.; Seiskari, T.; Aittoniemi, J.; Huttunen, R.; Syrjänen, J.; Pesu, M. Reduced plasma PCSK9 response in patients with bacteraemia is associated with mortality. J. Intern. Med., 2019, 286(5), 553-561.
[http://dx.doi.org/10.1111/joim.12946] [PMID: 31166632]
[22]
Schoergenhofer, C.; Matzneller, P.; Mühlbacher, J.; Hell, L.; Zeitlinger, M.; Jilma, B. PCSK9 decreases during experimental endotoxemia. J. Intern. Med., 2020, 287(3), 333-335.
[http://dx.doi.org/10.1111/joim.13003] [PMID: 31660669]
[23]
Vecchié, A.; Bonaventura, A.; Meessen, J.; Novelli, D.; Minetti, S.; Elia, E.; Ferrara, D.; Ansaldo, A.M.; Scaravilli, V.; Villa, S.; Ferla, L.; Caironi, P.; Latini, R.; Carbone, F.; Montecucco, F. PCSK9 is associated with mortality in patients with septic shock: data from the ALBIOS study. J. Intern. Med., 2021, 289(2), 179-192.
[http://dx.doi.org/10.1111/joim.13150] [PMID: 32686253]
[24]
Guo, Y.; Yan, B.; Gui, Y.; Tang, Z.; Tai, S.; Zhou, S.; Zheng, X.L. Physiology and role of PCSK9 in vascular disease: Potential impact of localized PCSK9 in vascular wall. J. Cell. Physiol., 2021, 236(4), 2333-2351.
[http://dx.doi.org/10.1002/jcp.30025] [PMID: 32875580]
[25]
Norata, G.D.; Tavori, H.; Pirillo, A.; Fazio, S.; Catapano, A.L. Biology of proprotein convertase subtilisin kexin 9: Beyond low-density lipoprotein cholesterol lowering. Cardiovasc. Res., 2016, 112(1), 429-442.
[http://dx.doi.org/10.1093/cvr/cvw194] [PMID: 27496869]
[26]
van Duijnhoven, F.J.; Bueno-De-Mesquita, H.B.; Calligaro, M.; Jenab, M.; Pischon, T.; Jansen, E.H.; Frohlich, J.; Ayyobi, A.; Overvad, K.; Toft-Petersen, A.P.; Tjønneland, A.; Hansen, L.; Boutron-Ruault, M.C.; Clavel-Chapelon, F.; Cottet, V.; Palli, D.; Tagliabue, G.; Panico, S.; Tumino, R.; Vineis, P.; Kaaks, R.; Teucher, B.; Boeing, H.; Drogan, D.; Trichopoulou, A.; Lagiou, P.; Dilis, V.; Peeters, P.H.; Siersema, P.D.; Rodríguez, L.; González, C.A.; Molina-Montes, E.; Dorronsoro, M.; Tormo, M.J.; Barricarte, A.; Palmqvist, R.; Hallmans, G.; Khaw, K.T.; Tsilidis, K.K.; Crowe, F.L.; Chajes, V.; Fedirko, V.; Rinaldi, S.; Norat, T.; Riboli, E. Blood lipid and lipoprotein concentrations and colorectal cancer risk in the European Prospective Investigation into Cancer and Nutrition. Gut, 2011, 60(8), 1094-1102.
[http://dx.doi.org/10.1136/gut.2010.225011] [PMID: 21383385]
[27]
Coppola, J.A.; Shrubsole, M.J.; Cai, Q.; Smalley, W.E.; Dai, Q.; Ness, R.M.; Fazio, S.; Zheng, W.; Murff, H.J. Plasma lipid levels and colorectal adenoma risk. Cancer Causes Control, 2015, 26(4), 635-643.
[http://dx.doi.org/10.1007/s10552-015-0555-y] [PMID: 25761410]
[28]
Guan, X.; Liu, Z.; Zhao, Z.; Zhang, X.; Tao, S.; Yuan, B.; Zhang, J.; Wang, D.; Liu, Q.; Ding, Y. Emerging roles of low-density lipoprotein in the development and treatment of breast cancer. Lipids Health Dis., 2019, 18(1), 137.
[http://dx.doi.org/10.1186/s12944-019-1075-7] [PMID: 31182104]
[29]
Ding, X.; Zhang, W.; Li, S.; Yang, H. The role of cholesterol metabolism in cancer. Am. J. Cancer Res., 2019, 9(2), 219-227.
[PMID: 30906624]
[30]
Cedó, L.; Reddy, S.T.; Mato, E.; Blanco-Vaca, F.; Escolà-Gil, J.C. HDL and LDL: potential new players in breast cancer development. J. Clin. Med., 2019, 8(6), 8.
[http://dx.doi.org/10.3390/jcm8060853] [PMID: 31208017]
[31]
Jacobs, D.; Blackburn, H.; Higgins, M.; Reed, D.; Iso, H.; McMillan, G.; Neaton, J.; Nelson, J.; Potter, J.; Rifkind, B. Report of the conference on low blood cholesterol: mortality associations. Circulation, 1992, 86(3), 1046-1060.
[http://dx.doi.org/10.1161/01.CIR.86.3.1046] [PMID: 1355411]
[32]
Law, M.R.; Thompson, S.G. Low serum cholesterol and the risk of cancer: an analysis of the published prospective studies. Cancer Causes Control, 1991, 2(4), 253-261.
[http://dx.doi.org/10.1007/BF00052142] [PMID: 1831389]
[33]
Folsom, A.R.; Peacock, J.M.; Boerwinkle, E. Sequence variation in proprotein convertase subtilisin/kexin type 9 serine protease gene, low LDL cholesterol, and cancer incidence. Cancer Epidemiol. Biomarkers Prev., 2007, 16(11), 2455-2458.
[http://dx.doi.org/10.1158/1055-9965.EPI-07-0502] [PMID: 18006936]
[34]
Benn, M.; Tybjærg-Hansen, A.; Stender, S.; Frikke-Schmidt, R.; Nordestgaard, B.G. Low-density lipoprotein cholesterol and the risk of cancer: a mendelian randomization study. J. Natl. Cancer Inst., 2011, 103(6), 508-519.
[http://dx.doi.org/10.1093/jnci/djr008] [PMID: 21285406]
[35]
Nowak, C.; Ärnlöv, J. A Mendelian randomization study of the effects of blood lipids on breast cancer risk. Nat. Commun., 2018, 9(1), 3957.
[http://dx.doi.org/10.1038/s41467-018-06467-9] [PMID: 30262900]
[36]
Carter, P.; Vithayathil, M.; Kar, S.; Potluri, R.; Mason, A.M.; Larsson, S.C.; Burgess, S. Predicting the effect of statins on cancer risk using genetic variants from a Mendelian randomization study in the UK Biobank. eLife, 2020, 9, 9.
[http://dx.doi.org/10.7554/eLife.57191] [PMID: 33046214]
[37]
Marimuthu, A.; Subbannayya, Y.; Sahasrabuddhe, N.A.; Balakrishnan, L.; Syed, N.; Sekhar, N.R.; Katte, T.V.; Pinto, S.M.; Srikanth, S.M.; Kumar, P.; Pawar, H.; Kashyap, M.K.; Maharudraiah, J.; Ashktorab, H.; Smoot, D.T.; Ramaswamy, G.; Kumar, R.V.; Cheng, Y.; Meltzer, S.J.; Roa, J.C.; Chaerkady, R.; Prasad, T.S.; Harsha, H.C.; Chatterjee, A.; Pandey, A. SILAC-based quantitative proteomic analysis of gastric cancer secretome. Proteomics Clin. Appl., 2013, 7(5-6), 355-366.
[http://dx.doi.org/10.1002/prca.201200069] [PMID: 23161554]
[38]
Xu, B.; Li, S.; Fang, Y.; Zou, Y.; Song, D.; Zhang, S.; Cai, Y. Proprotein Convertase Subtilisin/Kexin Type 9 promotes gastric cancer metastasis and suppresses apoptosis by facilitating MAPK signaling pathway through HSP70 up-regulation. Front. Oncol., 2021, 10, 609663.
[http://dx.doi.org/10.3389/fonc.2020.609663] [PMID: 33489919]
[39]
Ito, M.; Hiwasa, T.; Oshima, Y.; Yajima, S.; Suzuki, T.; Nanami, T.; Sumazaki, M.; Shiratori, F.; Funahashi, K.; Li, S.Y.; Iwadate, Y.; Yamagata, H.; Jambaljav, B.; Takemoto, M.; Yokote, K.; Takizawa, H.; Shimada, H. Association of serum anti-PCSK9 antibody levels with favorable postoperative prognosis in esophageal cancer. Front. Oncol., 2021, 11, 708039.
[http://dx.doi.org/10.3389/fonc.2021.708039] [PMID: 34504788]
[40]
Bhat, M.; Skill, N.; Marcus, V.; Deschenes, M.; Tan, X.; Bouteaud, J.; Negi, S.; Awan, Z.; Aikin, R.; Kwan, J.; Amre, R.; Tabaries, S.; Hassanain, M.; Seidah, N.G.; Maluccio, M.; Siegel, P.; Metrakos, P. Decreased PCSK9 expression in human hepatocellular carcinoma. BMC Gastroenterol., 2015, 15, 176.
[http://dx.doi.org/10.1186/s12876-015-0371-6] [PMID: 26674961]
[41]
He, M.; Hu, J.; Fang, T.; Tang, W.; Lv, B.; Yang, B.; Xia, J. Protein convertase subtilisin/Kexin type 9 inhibits hepatocellular carcinoma growth by interacting with GSTP1 and suppressing the JNK signaling pathway. Cancer Biol. Med., 2021.
[http://dx.doi.org/10.20892/j.issn.2095-3941.2020.0313] [PMID: 33893729]
[42]
Athavale, D.; Chouhan, S.; Pandey, V.; Mayengbam, S.S.; Singh, S.; Bhat, M.K. Hepatocellular carcinoma-associated hypercholesterolemia: involvement of proprotein-convertase-subtilisin-kexin type-9 (PCSK9). Cancer Metab., 2018, 6, 16.
[http://dx.doi.org/10.1186/s40170-018-0187-2] [PMID: 30386595]
[43]
Zhang, S.Z.; Zhu, X.D.; Feng, L.H.; Li, X.L.; Liu, X.F.; Sun, H.C.; Tang, Z.Y. PCSK9 promotes tumor growth by inhibiting tumor cell apoptosis in hepatocellular carcinoma. Exp. Hematol. Oncol., 2021, 10(1), 25.
[http://dx.doi.org/10.1186/s40164-021-00218-1] [PMID: 33789749]
[44]
Sun, X.; Essalmani, R.; Day, R.; Khatib, A.M.; Seidah, N.G.; Prat, A. Proprotein convertase subtilisin/kexin type 9 deficiency reduces melanoma metastasis in liver. Neoplasia, 2012, 14(12), 1122-1131.
[http://dx.doi.org/10.1593/neo.121252] [PMID: 23308045]
[45]
Xu, X.; Cui, Y.; Cao, L.; Zhang, Y.; Yin, Y.; Hu, X. PCSK9 regulates apoptosis in human lung adenocarcinoma A549 cells via endoplasmic reticulum stress and mitochondrial signaling pathways. Exp. Ther. Med., 2017, 13(5), 1993-1999.
[http://dx.doi.org/10.3892/etm.2017.4218] [PMID: 28565798]
[46]
Naseri, M.H.; Mahdavi, M.; Davoodi, J.; Tackallou, S.H.; Goudarzvand, M.; Neishabouri, S.H. Up regulation of Bax and down regulation of Bcl2 during 3-NC mediated apoptosis in human cancer cells. Cancer Cell Int., 2015, 15, 55.
[http://dx.doi.org/10.1186/s12935-015-0204-2] [PMID: 26074734]
[47]
Suh, J.M.; Son, Y.; Yoo, J.Y.; Goh, Y.; Seidah, N.G.; Lee, S.; Bae, Y.S. Proprotein convertase subtilisin/kexin Type 9 is required for Ahnak-mediated metastasis of melanoma into lung epithelial cells. Neoplasia, 2021, 23(9), 993-1001.
[http://dx.doi.org/10.1016/j.neo.2021.07.007] [PMID: 34352405]
[48]
Bonaventura, A.; Grossi, F.; Carbone, F.; Vecchié, A.; Minetti, S.; Bardi, N.; Elia, E.; Ansaldo, A.M.; Ferrara, D.; Rijavec, E.; Dal Bello, M.G.; Rossi, G.; Biello, F.; Tagliamento, M.; Alama, A.; Coco, S.; Spallarossa, P.; Dallegri, F.; Genova, C.; Montecucco, F. Serum PCSK9 levels at the second nivolumab cycle predict overall survival in elderly patients with NSCLC: a pilot study. Cancer Immunol. Immunother., 2019, 68(8), 1351-1358.
[http://dx.doi.org/10.1007/s00262-019-02367-z] [PMID: 31327024]
[49]
Bonaventura, A.; Grossi, F.; Montecucco, F. PCSK9 is a promising prognostic marker in patients with advanced NSCLC. Cancer Immunol. Immunother., 2020, 69(3), 491-492.
[http://dx.doi.org/10.1007/s00262-020-02485-z] [PMID: 31938855]
[50]
Gan, S.S.; Ye, J.Q.; Wang, L.; Qu, F.J.; Chu, C.M.; Tian, Y.J.; Yang, W.; Cui, X.G. Inhibition of PCSK9 protects against radiation-induced damage of prostate cancer cells. OncoTargets Ther., 2017, 10, 2139-2146.
[http://dx.doi.org/10.2147/OTT.S129413] [PMID: 28442922]
[51]
Cheng, M.; Watson, P.H.; Paterson, J.A.; Seidah, N.; Chrétien, M.; Shiu, R.P. Pro-protein convertase gene expression in human breast cancer. Int. J. Cancer, 1997, 71(6), 966-971.
[http://dx.doi.org/10.1002/(SICI)1097-0215(19970611)71:6<966:AID-IJC10>3.0.CO;2-4] [PMID: 9185698]
[52]
Abdelwahed, K.S.; Siddique, A.B.; Mohyeldin, M.M.; Qusa, M.H.; Goda, A.A.; Singh, S.S.; Ayoub, N.M.; King, J.A.; Jois, S.D.; El Sayed, K.A. Pseurotin A as a novel suppressor of hormone dependent breast cancer progression and recurrence by inhibiting PCSK9 secretion and interaction with LDL receptor. Pharmacol. Res., 2020, 158, 104847.
[http://dx.doi.org/10.1016/j.phrs.2020.104847] [PMID: 32438039]
[53]
Llaverias, G.; Danilo, C.; Mercier, I.; Daumer, K.; Capozza, F.; Williams, T.M.; Sotgia, F.; Lisanti, M.P.; Frank, P.G. Role of cholesterol in the development and progression of breast cancer. Am. J. Pathol., 2011, 178(1), 402-412.
[http://dx.doi.org/10.1016/j.ajpath.2010.11.005] [PMID: 21224077]
[54]
Torre, L.A.; Trabert, B.; DeSantis, C.E.; Miller, K.D.; Samimi, G.; Runowicz, C.D.; Gaudet, M.M.; Jemal, A.; Siegel, R.L. Ovarian cancer statistics, 2018. CA Cancer J. Clin., 2018, 68(4), 284-296.
[http://dx.doi.org/10.3322/caac.21456] [PMID: 29809280]
[55]
Ruscica, M.; Botta, M.; Ferri, N.; Giorgio, E.; Macchi, C.; Franceschini, G.; Magni, P.; Calabresi, L.; Gomaraschi, M. High density lipoproteins inhibit oxidative stress-induced prostate cancer cell proliferation. Sci. Rep., 2018, 8(1), 2236.
[http://dx.doi.org/10.1038/s41598-018-19568-8] [PMID: 29396407]
[56]
Röhrig, F.; Schulze, A. The multifaceted roles of fatty acid synthesis in cancer. Nat. Rev. Cancer, 2016, 16(11), 732-749.
[http://dx.doi.org/10.1038/nrc.2016.89] [PMID: 27658529]
[57]
Tudrej, P.; Olbryt, M.; Zembala-Nożyńska, E.; Kujawa, K.A.; Cortez, A.J.; Fiszer-Kierzkowska, A.; Pigłowski, W.; Nikiel, B.; Głowala-Kosińska, M.; Bartkowska-Chrobok, A.; Smagur, A.; Fidyk, W.; Lisowska, K.M. Establishment and characterization of the novel high-grade serous ovarian cancer cell line OVPA8. Int. J. Mol. Sci., 2018, 19(7), 19.
[http://dx.doi.org/10.3390/ijms19072080] [PMID: 30018258]
[58]
Jacome Sanz, D.; Raivola, J.; Karvonen, H.; Arjama, M.; Barker, H.; Murumägi, A.; Ungureanu, D. Evaluating targeted therapies in ovarian cancer metabolism: novel role for PCSK9 and second generation mTOR inhibitors. Cancers (Basel), 2021, 13(15), 13.
[http://dx.doi.org/10.3390/cancers13153727] [PMID: 34359627]
[59]
Almeida, C.R.; Ferreira, B.H.; Duarte, I.F. Targeting PCSK9: A promising adjuvant strategy in cancer immunotherapy. Signal Transduct. Target. Ther., 2021, 6(1), 111.
[http://dx.doi.org/10.1038/s41392-021-00530-6] [PMID: 33677469]
[60]
Liu, X.; Bao, X.; Hu, M.; Chang, H.; Jiao, M.; Cheng, J.; Xie, L.; Huang, Q.; Li, F.; Li, C.Y. Inhibition of PCSK9 potentiates immune checkpoint therapy for cancer. Nature, 2020, 588(7839), 693-698.
[http://dx.doi.org/10.1038/s41586-020-2911-7] [PMID: 33177715]
[61]
Yuan, J.; Cai, T.; Zheng, X.; Ren, Y.; Qi, J.; Lu, X.; Chen, H.; Lin, H.; Chen, Z.; Liu, M.; He, S.; Chen, Q.; Feng, S.; Wu, Y.; Zhang, Z.; Ding, Y.; Yang, W. Potentiating CD8+ T cell antitumor activity by inhibiting PCSK9 to promote LDLR-mediated TCR recycling and signaling. Protein Cell, 2021, 12(4), 240-260.
[http://dx.doi.org/10.1007/s13238-021-00821-2] [PMID: 33606190]
[62]
Nurmohamed, N.S.; Navar, A.M.; Kastelein, J.J.P. New and emerging therapies for reduction of LDL-cholesterol and apolipoprotein B: JACC focus seminar 1/4. J. Am. Coll. Cardiol., 2021, 77(12), 1564-1575.
[http://dx.doi.org/10.1016/j.jacc.2020.11.079] [PMID: 33766264]
[63]
Kosmas, C.E.; Skavdis, A.; Sourlas, A.; Papakonstantinou, E.J.; Peña Genao, E.; Echavarria Uceta, R.; Guzman, E. Safety and tolerability of PCSK9 inhibitors: current insights. Clin. Pharmacol., 2020, 12, 191-202.
[http://dx.doi.org/10.2147/CPAA.S288831] [PMID: 33335431]
[64]
Ball, S.; Ghosh, R.K.; Wongsaengsak, S.; Bandyopadhyay, D.; Ghosh, G.C.; Aronow, W.S.; Fonarow, G.C.; Lenihan, D.J.; Bhatt, D.L. Cardiovascular toxicities of immune checkpoint inhibitors: JACC review topic of the week. J. Am. Coll. Cardiol., 2019, 74(13), 1714-1727.
[http://dx.doi.org/10.1016/j.jacc.2019.07.079] [PMID: 31558256]
[65]
Wright, J.J.; Powers, A.C.; Johnson, D.B. Endocrine toxicities of immune checkpoint inhibitors. Nat. Rev. Endocrinol., 2021, 17(7), 389-399.
[http://dx.doi.org/10.1038/s41574-021-00484-3] [PMID: 33875857]
[66]
Marin-Acevedo, J.A.; Chirila, R.M.; Dronca, R.S. Immune checkpoint inhibitor toxicities. Mayo Clin. Proc., 2019, 94(7), 1321-1329.
[http://dx.doi.org/10.1016/j.mayocp.2019.03.012] [PMID: 31272574]
[67]
Fattori, E.; Cappelletti, M.; Lo Surdo, P.; Calzetta, A.; Bendtsen, C.; Ni, Y.G.; Pandit, S.; Sitlani, A.; Mesiti, G.; Carfí, A.; Monaci, P. Immunization against proprotein convertase subtilisin-like/kexin type 9 lowers plasma LDL-cholesterol levels in mice. J. Lipid Res., 2012, 53(8), 1654-1661.
[http://dx.doi.org/10.1194/jlr.M028340] [PMID: 22611251]
[68]
Crossey, E.; Amar, M.J.A.; Sampson, M.; Peabody, J.; Schiller, J.T.; Chackerian, B.; Remaley, A.T. A cholesterol-lowering VLP vaccine that targets PCSK9. Vaccine, 2015, 33(43), 5747-5755.
[http://dx.doi.org/10.1016/j.vaccine.2015.09.044] [PMID: 26413878]
[69]
Landlinger, C.; Pouwer, M.G.; Juno, C.; van der Hoorn, J.W.A.; Pieterman, E.J.; Jukema, J.W.; Staffler, G.; Princen, H.M.G.; Galabova, G. The AT04A vaccine against proprotein convertase subtilisin/kexin type 9 reduces total cholesterol, vascular inflammation, and atherosclerosis in APOE*3Leiden.CETP mice. Eur. Heart J., 2017, 38(32), 2499-2507.
[http://dx.doi.org/10.1093/eurheartj/ehx260] [PMID: 28637178]
[70]
Galabova, G.; Brunner, S.; Winsauer, G.; Juno, C.; Wanko, B.; Mairhofer, A.; Lührs, P.; Schneeberger, A.; von Bonin, A.; Mattner, F.; Schmidt, W.; Staffler, G. Peptide-based anti-PCSK9 vaccines - an approach for long-term LDLc management. PLoS One, 2014, 9(12), e114469.
[http://dx.doi.org/10.1371/journal.pone.0114469] [PMID: 25474576]
[71]
Momtazi-Borojeni, A.A.; Jaafari, M.R.; Badiee, A.; Sahebkar, A. Long-term generation of antiPCSK9 antibody using a nanoliposome-based vaccine delivery system. Atherosclerosis, 2019, 283, 69-78.
[http://dx.doi.org/10.1016/j.atherosclerosis.2019.02.001] [PMID: 30797988]
[72]
Sahebkar, A.; Momtazi-Borojeni, A.A.; Banach, M. PCSK9 vaccine: so near, yet so far! Eur. Heart J., 2021, 2021, ehab299.
[http://dx.doi.org/10.1093/eurheartj/ehab299] [PMID: 34151957]
[73]
Momtazi-Borojeni, A.A.; Nik, M.E.; Jaafari, M.R.; Banach, M.; Sahebkar, A. Effects of immunization against PCSK9 in an experimental model of breast cancer. Arch. Med. Sci., 2019, 15(3), 570-579.
[http://dx.doi.org/10.5114/aoms.2019.84734] [PMID: 31110521]
[74]
Momtazi-Borojeni, A.A.; Nik, M.E.; Jaafari, M.R.; Banach, M.; Sahebkar, A. Effects of immunisation against PCSK9 in mice bearing melanoma. Arch. Med. Sci., 2019, 16(1), 189-199.
[http://dx.doi.org/10.5114/aoms.2020.91291] [PMID: 32051723]
[75]
Toth, S.; Pella, D.; Fedacko, J. Vaccines targeting PSCK9 for the treatment of hyperlipidemia. Cardiol. Ther., 2020, 9(2), 323-332.
[http://dx.doi.org/10.1007/s40119-020-00191-6] [PMID: 32737796]
[76]
Ruscica, M.; Tokgözoğlu, L.; Corsini, A.; Sirtori, C.R. PCSK9 inhibition and inflammation: a narrative review. Atherosclerosis, 2019, 288, 146-155.
[http://dx.doi.org/10.1016/j.atherosclerosis.2019.07.015] [PMID: 31404822]
[77]
Persson, L.; Cao, G.; Ståhle, L.; Sjöberg, B.G.; Troutt, J.S.; Konrad, R.J.; Gälman, C.; Wallén, H.; Eriksson, M.; Hafström, I.; Lind, S.; Dahlin, M.; Amark, P.; Angelin, B.; Rudling, M. Circulating proprotein convertase subtilisin kexin type 9 has a diurnal rhythm synchronous with cholesterol synthesis and is reduced by fasting in humans. Arterioscler. Thromb. Vasc. Biol., 2010, 30(12), 2666-2672.
[http://dx.doi.org/10.1161/ATVBAHA.110.214130] [PMID: 20884874]
[78]
Lakoski, S.G.; Lagace, T.A.; Cohen, J.C.; Horton, J.D.; Hobbs, H.H. Genetic and metabolic determinants of plasma PCSK9 levels. J. Clin. Endocrinol. Metab., 2009, 94(7), 2537-2543.
[http://dx.doi.org/10.1210/jc.2009-0141] [PMID: 19351729]
[79]
Ferri, N.; Ruscica, M.; Coggi, D.; Bonomi, A.; Amato, M.; Frigerio, B.; Sansaro, D.; Ravani, A.; Veglia, F.; Capra, N.; Lupo, M.G.; Macchi, C.; Castelnuovo, S.; Savonen, K.; Silveira, A.; Kurl, S.; Giral, P.; Pirro, M.; Strawbridge, R.J.; Gigante, B.; Smit, A.J.; Tremoli, E.; Colombo, G.I.; Baldassarre, D. Sex-specific predictors of PCSK9 levels in a European population: The IMPROVE study. Atherosclerosis, 2020, 309, 39-46.
[http://dx.doi.org/10.1016/j.atherosclerosis.2020.07.014] [PMID: 32862087]
[80]
Costet, P.; Cariou, B.; Lambert, G.; Lalanne, F.; Lardeux, B.; Jarnoux, A.L.; Grefhorst, A.; Staels, B.; Krempf, M. Hepatic PCSK9 expression is regulated by nutritional status via insulin and sterol regulatory element-binding protein 1c. J. Biol. Chem., 2006, 281(10), 6211-6218.
[http://dx.doi.org/10.1074/jbc.M508582200] [PMID: 16407292]

Rights & Permissions Print Cite
Article Metrics
25
1
© 2024 Bentham Science Publishers | Privacy Policy