YAP1 overexpression contributes to the development of enzalutamide resistance by induction of cancer stemness and lipid metabolism in prostate cancer.
Adaptor Proteins, Signal Transducing
/ genetics
Aged
Animals
Benzamides
/ administration & dosage
COUP Transcription Factor II
/ genetics
Cell Movement
/ drug effects
Cell Proliferation
/ drug effects
Drug Resistance, Neoplasm
/ drug effects
Gene Expression Regulation, Neoplastic
/ drug effects
Heterografts
Humans
Lipid Metabolism
/ drug effects
Male
Mice
MicroRNAs
/ genetics
Middle Aged
Neoplastic Stem Cells
/ drug effects
Nitriles
/ administration & dosage
Phenylthiohydantoin
/ administration & dosage
Prostatic Neoplasms
/ drug therapy
Transcription Factors
/ genetics
YAP-Signaling Proteins
Journal
Oncogene
ISSN: 1476-5594
Titre abrégé: Oncogene
Pays: England
ID NLM: 8711562
Informations de publication
Date de publication:
04 2021
04 2021
Historique:
received:
29
05
2020
accepted:
15
02
2021
revised:
03
02
2021
pubmed:
6
3
2021
medline:
21
10
2021
entrez:
5
3
2021
Statut:
ppublish
Résumé
Metastatic castration-resistant prostate cancer (mCRPC) is a malignant and lethal disease caused by relapse after androgen-deprivation (ADT) therapy. Since enzalutamide is innovated and approved by US FDA as a new treatment option for mCRPC patients, drug resistance for enzalutamide is a critical issue during clinical usage. Although several underlying mechanisms causing enzalutamide resistance were previously identified, most of them revealed that drug resistant cells are still highly addicted to androgen and AR functions. Due to the numerous physical functions of AR in men, innovated AR-independent therapy might alleviate enzalutamide resistance and prevent production of adverse side effects. Here, we have identified that yes-associated protein 1 (YAP1) is overexpressed in enzalutamide-resistant (EnzaR) cells. Furthermore, enzalutamide-induced YAP1 expression is mediated through the function of chicken ovalbumin upstream promoter transcription factor 2 (COUP-TFII) at the transcriptional and the post-transcriptional levels. Functional analyses reveal that YAP1 positively regulates numerous genes related to cancer stemness and lipid metabolism and interacts with COUP-TFII to form a transcriptional complex. More importantly, YAP1 inhibitor attenuates the growth and cancer stemness of EnzaR cells in vitro and in vivo. Finally, YAP1, COUP-TFII, and miR-21 are detected in the extracellular vesicles (EVs) isolated from EnzaR cells and sera of patients. In addition, treatment with EnzaR-EVs induces the abilities of cancer stemness, lipid metabolism and enzalutamide resistance in its parental cells. Taken together, these results suggest that YAP1 might be a crucial factor involved in the development of enzalutamide resistance and can be an alternative therapeutic target in prostate cancer.
Identifiants
pubmed: 33664454
doi: 10.1038/s41388-021-01718-4
pii: 10.1038/s41388-021-01718-4
pmc: PMC8016667
doi:
Substances chimiques
Adaptor Proteins, Signal Transducing
0
Benzamides
0
COUP Transcription Factor II
0
MIRN21 microRNA, human
0
MicroRNAs
0
NR2F2 protein, human
0
Nitriles
0
Transcription Factors
0
YAP-Signaling Proteins
0
YAP1 protein, human
0
Phenylthiohydantoin
2010-15-3
enzalutamide
93T0T9GKNU
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2407-2421Commentaires et corrections
Type : ErratumIn
Références
Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, et al. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer. 2015;136:E359–386.
doi: 10.1002/ijc.29210
Klein EA, Ciezki J, Kupelian PA, Mahadevan A. Outcomes for intermediate risk PCa: are there advantages for surgery, external radiation, or brachytherapy? Urol Oncol. 2009;27:67–71.
doi: 10.1016/j.urolonc.2008.04.001
Lukka H, Waldron T, Klotz L, Winquist E, Trachtenberg J, Genitourinary Cancer Disease Site G et al. Maximal androgen blockade for the treatment of metastatic PCa–a systematic review. Curr Oncol. 2006;13:81–93.
Tannock IF, de Wit R, Berry WR, Horti J, Pluzanska A, Chi KN, et al. Docetaxel plus prednisone or mitoxantrone plus prednisone for advanced PCa. N. Engl J Med. 2004;351:1502–12.
doi: 10.1056/NEJMoa040720
Petrylak DP, Tangen CM, Hussain MH, Lara PN Jr., Jones JA, Taplin ME, et al. Docetaxel and estramustine compared with mitoxantrone and prednisone for advanced refractory PCa. N. Engl J Med. 2004;351:1513–20.
doi: 10.1056/NEJMoa041318
de Bono JS, Logothetis CJ, Molina A, Fizazi K, North S, Chu L, et al. Abiraterone and increased survival in metastatic PCa. N. Engl J Med. 2011;364:1995–2005.
doi: 10.1056/NEJMoa1014618
Scher HI, Fizazi K, Saad F, Taplin ME, Sternberg CN, Miller K, et al. Increased survival with enzalutamide in PCa after chemotherapy. N. Engl J Med. 2012;367:1187–97.
doi: 10.1056/NEJMoa1207506
Ning YM, Brave M, Maher VE, Zhang L, Tang S, Sridhara R, et al. U.S. food and drug administration approval summary: enzalutamide for the treatment of patients with chemotherapy-naive metastatic castration-resistant PCa. Oncologist. 2015;20:960–6.
doi: 10.1634/theoncologist.2015-0166
Hussain M, Fizazi K, Saad F, Rathenborg P, Shore N, Ferreira U, et al. Enzalutamide in men with nonmetastatic, castration-resistant PCa. N. Engl J Med. 2018;378:2465–74.
doi: 10.1056/NEJMoa1800536
Korpal M, Korn JM, Gao X, Rakiec DP, Ruddy DA, Doshi S, et al. An F876L mutation in androgen receptor confers genetic and phenotypic resistance to MDV3100 (enzalutamide). Cancer Discov. 2013;3:1030–43.
doi: 10.1158/2159-8290.CD-13-0142
Arora VK, Schenkein E, Murali R, Subudhi SK, Wongvipat J, Balbas MD, et al. Glucocorticoid receptor confers resistance to antiandrogens by bypassing androgen receptor blockade. Cell. 2013;155:1309–22.
doi: 10.1016/j.cell.2013.11.012
Antonarakis ES, Lu C, Wang H, Luber B, Nakazawa M, Roeser JC, et al. AR-V7 and resistance to enzalutamide and abiraterone in PCa. N. Engl J Med. 2014;371:1028–38.
doi: 10.1056/NEJMoa1315815
Coutinho I, Day TK, Tilley WD, Selth LA. Androgen receptor signaling in castration-resistant PCa: a lesson in persistence. Endocr Relat Cancer. 2016;23:T179–T197.
doi: 10.1530/ERC-16-0422
Harvey KF, Zhang X, Thomas DM. The Hippo pathway and human cancer. Nat Rev Cancer. 2013;13:246–57.
doi: 10.1038/nrc3458
Dong J, Feldmann G, Huang J, Wu S, Zhang N, Comerford SA, et al. Elucidation of a universal size-control mechanism in Drosophila and mammals. Cell. 2007;130:1120–33.
doi: 10.1016/j.cell.2007.07.019
Zhao B, Wei X, Li W, Udan RS, Yang Q, Kim J, et al. Inactivation of YAP oncoprotein by the Hippo pathway is involved in cell contact inhibition and tissue growth control. Genes Dev. 2007;21:2747–61.
doi: 10.1101/gad.1602907
Tumaneng K, Russell RC, Guan KL. Organ size control by Hippo and TOR pathways. Curr Biol. 2012;22:R368–79.
doi: 10.1016/j.cub.2012.03.003
Nguyen LT, Tretiakova MS, Silvis MR, Lucas J, Klezovitch O, Coleman I, et al. ERG activates the YAP1 transcriptional program and induces the development of age-related prostate tumors. Cancer Cell. 2015;27:797–808.
doi: 10.1016/j.ccell.2015.05.005
Jiang N, Hjorth-Jensen K, Hekmat O, Iglesias-Gato D, Kruse T, Wang C, et al. In vivo quantitative phosphoproteomic profiling identifies novel regulators of castration-resistant PCa growth. Oncogene. 2015;34:2764–76.
doi: 10.1038/onc.2014.206
Zhang L, Yang S, Chen X, Stauffer S, Yu F, Lele SM, et al. The hippo pathway effector YAP regulates motility, invasion, and castration-resistant growth of PCa cells. Mol Cell Biol. 2015;35:1350–62.
doi: 10.1128/MCB.00102-15
Kuser-Abali G, Alptekin A, Lewis M, Garraway IP, Cinar BYAP1. and AR interactions contribute to the switch from androgen-dependent to castration-resistant growth in PCa. Nat Commun. 2015;6:8126.
doi: 10.1038/ncomms9126
Lin SC, Kao CY, Lee HJ, Creighton CJ, Ittmann MM, Tsai SJ, et al. Dysregulation of miRNAs-COUP-TFII-FOXM1-CENPF axis contributes to the metastasis of PCa. Nat Commun. 2016;7:11418.
doi: 10.1038/ncomms11418
Li H, Feng Z, He ML. Lipid metabolism alteration contributes to and maintains the properties of cancer stem cells. Theranostics. 2020;10:7053–69.
doi: 10.7150/thno.41388
Zadra G, Ribeiro CF, Chetta P, Ho Y, Cacciatore S, Gao X, et al. Inhibition of de novo lipogenesis targets androgen receptor signaling in castration-resistant PCa. Proc Natl Acad Sci USA. 2019;116:631–40.
doi: 10.1073/pnas.1808834116
Abudurexiti M, Zhu W, Wang Y, Wang J, Xu W, Huang Y, et al. Targeting CPT1B as a potential therapeutic strategy in castration-resistant and enzalutamide-resistant PCa. Prostate. 2020;80:950–61.
doi: 10.1002/pros.24027
Liu-Chittenden Y, Huang B, Shim JS, Chen Q, Lee SJ, Anders RA, et al. Genetic and pharmacological disruption of the TEAD-YAP complex suppresses the oncogenic activity of YAP. Genes Dev. 2012;26:1300–5.
doi: 10.1101/gad.192856.112
Beer TM, Armstrong AJ, Rathkopf DE, Loriot Y, Sternberg CN, Higano CS, et al. Enzalutamide in metastatic PCa before chemotherapy. N. Engl J Med. 2014;371:424–33.
doi: 10.1056/NEJMoa1405095
Miyazawa Y, Sekine Y, Shimizu N, Takezawa Y, Nakamura T, Miyao T, et al. An exploratory retrospective multicenter study of prognostic factors in mCRPC patients undergoing enzalutamide treatment: Focus on early PSA decline and kinetics at time of progression. Prostate. 2019;79:1462–70.
doi: 10.1002/pros.23865
Jiang N, Ke B, Hjort-Jensen K, Iglesias-Gato D, Wang Z, Chang P, et al. YAP1 regulates PCa stem cell-like characteristics to promote castration resistant growth. Oncotarget. 2017;8:115054–67.
doi: 10.18632/oncotarget.23014
Stoykova GE, Schlaepfer IR. Lipid metabolism and endocrine resistance in PCa, and new opportunities for therapy. Int J Mol Sci. 2019;20:2626.
doi: 10.3390/ijms20112626
Kong Y, Cheng L, Mao F, Zhang Z, Zhang Y, Farah E, et al. Inhibition of cholesterol biosynthesis overcomes enzalutamide resistance in castration-resistant PCa (CRPC). J Biol Chem. 2018;293:14328–41.
doi: 10.1074/jbc.RA118.004442
Zhang Z, Zhou C, Li X, Barnes SD, Deng S, Hoover E, et al. Loss of CHD1 promotes heterogeneous mechanisms of resistance to AR-targeted therapy via chromatin dysregulation. Cancer Cell. 2020;37:584–98.e511.
doi: 10.1016/j.ccell.2020.03.001
Wang LCC-M, Qin J, Xu M, Kao C-Y, Shi J, You E, et al. Small-molecule inhibitor targeting orphan nuclear receptor COUP-TFII for PCa treatment. Sci Adv. 2020;6:eaaz8031.
doi: 10.1126/sciadv.aaz8031
Brave M, Weinstock C, Brewer JR, Chi DC, Suzman DL, Cheng J, et al. An FDA review of drug development in non-metastatic castration-resistant PCa. Clin Cancer Res. 2020;26:4717–22.
doi: 10.1158/1078-0432.CCR-19-3835
Borgmann H, Lallous N, Ozistanbullu D, Beraldi E, Paul N, Dalal K, et al. Moving towards precision urologic oncology: targeting enzalutamide-resistant PCa and mutated forms of the androgen receptor using the novel inhibitor darolutamide (ODM-201). Eur Urol. 2018;73:4–8.
doi: 10.1016/j.eururo.2017.08.012
Bainbridge A, Walker S, Smith J, Patterson K, Dutt A, Ng YM, et al. IKBKE activity enhances AR levels in advanced PCa via modulation of the Hippo pathway. Nucleic Acids Res. 2020;48:5366–82.
doi: 10.1093/nar/gkaa271
Cerasuolo M, Maccarinelli F, Coltrini D, Mahmoud AM, Marolda V, Ghedini GC, et al. Modeling acquired resistance to the second-generation androgen receptor antagonist enzalutamide in the TRAMP model of PCa. Cancer Res. 2020;80:1564–77.
doi: 10.1158/0008-5472.CAN-18-3637
Henry N, Sebe P, Cussenot O. Inappropriate treatment of PCa caused by heterophilic antibody interference. Nat Clin Pr Urol. 2009;6:164–7.
Abel S, Renz P, Hasan S, White R, Dawodu D, Wegner RE, et al. Alternative medicine and oncology: erroneous biochemical failure following herbal supplementation in early-stage PCa. J Am Osteopath Assoc. 2019;119:763–7.
pubmed: 31657830
pmcid: 7409554
Yanez-Mo M, Siljander PR, Andreu Z, Zavec AB, Borras FE, Buzas EI, et al. Biological properties of extracellular vesicles and their physiological functions. J Extracell Vesicles. 2015;4:27066.
doi: 10.3402/jev.v4.27066
Del ReM, Biasco E, Crucitta S, Derosa L, Rofi E, Orlandini C, et al. The detection of androgen receptor splice variant 7 in plasma-derived exosomal RNA strongly predicts resistance to hormonal therapy in metastatic PCa patients. Eur Urol. 2017;71:680–7.
doi: 10.1016/j.eururo.2016.08.012
Peak TC, Panigrahi GK, Praharaj PP, Su Y, Shi L, Chyr J, et al. Syntaxin 6-mediated exosome secretion regulates enzalutamide resistance in PCa. Mol Carcinog. 2020;59:62–72.
doi: 10.1002/mc.23129