Androgen Receptor-Dependent Mechanisms Mediating Drug Resistance in Prostate Cancer
Abstract
:Simple Summary
Abstract
1. Introduction
1.1. Role of AR in PCa and its Inhibition of AR in PCa Therapy
1.2. Genomic Action of AR
1.3. AR Gene Amplification, Mutations and AR Splice Variants
1.4. Co-Regulators of AR
1.5. Non-Genomic Action of AR
1.6. Bypass-Mechanisms of Aberrant Androgen Action to Activate AR Signaling Activation
1.7. Intratumoral and Alternative Androgen Biosynthesis
1.8. Role of Autophagy in AR-Dependent Drug Resistance
1.9. AR-Bypass Mechanisms to Mediate Castration Resistance
1.10. Non‑Coding RNAs and Drug Resistance in PCa
1.11. Role of Cytokines and Growth Factors in AR Signaling
2. Conclusions
Author Contributions
Funding
Conflicts of Interest
Abbreviations
AR | androgen receptor |
AR-V7 | an AR splice variant |
ADT | androgen deprivation therapy |
ARE | androgen response element |
Bic | bicalutamide |
CAF | cancer-associated fibroblasts |
CRPC | castration-resistant prostate cancer |
CTC | circulating tumor cells |
CSC | cancer stem cell |
DRPC | drug resistance Pca |
DHT | dihydrotestosterone |
EGFR | epidermal growth factor receptor |
Enz | enzalutamide |
EMT | epithelial-mesenchymal transition |
GR | glucocorticoid receptor |
LCoR | ligand-dependent co-repressor |
mCRPC | metastatic CRPC |
NLS | nuclear localization signal |
NEPC | neuroendocrine prostate cancer |
LBD | ligand-binding domain |
NTD | amino-terminal domain |
ODM | darolutamide |
Pca | prostate cancer |
PSA | prostate specific antigen |
SFK | Src family of kinases |
References
- Siegel, R.L.; Miller, K.D.; Fuchs, H.E.; Jemal, A. Cancer Statistics, 2021. CA Cancer J. Clin. 2021, 71, 7–33. [Google Scholar]
- Koivisto, P.; Kolmer, M.; Visakorpi, T.; Kallioniemi, O.-P. Androgen Receptor Gene and Hormonal Therapy Failure of Prostate Cancer. Am. J. Pathol. 1998, 152, 1. [Google Scholar]
- Vander Ark, A.; Woodford, E.; Li, X. Molecular Mechanisms of Therapies for Prostate Cancer with Bone Metastasis. J. Explor. Res. Pharmacol. 2016, 1, 35–39. [Google Scholar]
- Crawford, E.D.; Heidenreich, A.; Lawrentschuk, N.; Tombal, B.; Pompeo, A.C.; Mendoza-Valdes, A.; Miller, K.; Debruyne, F.M.; Klotz, L. Androgen-Targeted Therapy in Men with Prostate Cancer: Evolving Practice and Future Considerations. Prostate Cancer Prostatic Dis. 2019, 22, 24–38. [Google Scholar] [CrossRef] [Green Version]
- Maitland, N.J. Resistance to Antiandrogens in Prostate Cancer: Is It Inevitable, Intrinsic or Induced? Cancers 2021, 13, 327. [Google Scholar] [CrossRef]
- Schweizer, M.T.; Antonarakis, E.S.; Wang, H.; Ajiboye, A.S.; Spitz, A.; Cao, H.; Luo, J.; Haffner, M.C.; Yegnasubramanian, S.; Carducci, M.A.; et al. Effect of Bipolar Androgen Therapy for Asymptomatic Men with Castration-Resistant Prostate Cancer: Results from a Pilot Clinical Study. Sci. Transl. Med. 2015, 7, ra2–ra69. [Google Scholar] [CrossRef] [Green Version]
- Hussain, M.; Fizazi, K.; Saad, F.; Rathenborg, P.; Shore, N.; Ferreira, U.; Ivashchenko, P.; Demirhan, E.; Modelska, K.; Phung, D.; et al. Enzalutamide in Men with Nonmetastatic, Castration-Resistant Prostate Cancer. N. Engl. J. Med. 2018, 378, 2465–2474. [Google Scholar] [CrossRef]
- Fizazi, K.; Shore, N.; Tammela, T.L.; Ulys, A.; Vjaters, E.; Polyakov, S.; Jievaltas, M.; Luz, M.; Alekseev, B.; Kuss, I.; et al. Darolutamide in Nonmetastatic, Castration-Resistant Prostate Cancer. N. Engl. J. Med. 2019, 380, 1235–1246. [Google Scholar] [CrossRef] [PubMed]
- Gelman, I.H. Androgen Receptor Activation in Castration-Recurrent Prostate Cancer: The Role of Src-Family and Ack1 Tyrosine Kinases. Int. J. Biol. Sci. 2014, 10, 620. [Google Scholar] [CrossRef] [PubMed]
- Chandrasekar, T.; Yang, J.C.; Gao, A.C.; Evans, C.P. Mechanisms of Resistance in Castration-Resistant Prostate Cancer (Crpc). Transl. Androl. Urol. 2015, 4, 365. [Google Scholar] [PubMed]
- Hessenkemper, W.; Roediger, J.; Bartsch, S.; Houtsmuller, A.B.; van Royen, M.E.; Petersen, I.; Grimm, M.-O.; Baniahmad, A. A Natural Androgen Receptor Antagonist Induces Cellular Senescence in Prostate Cancer Cells. Mol. Endocrinol. 2014, 28, 1831–1840. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Kokal, M.; Mirzakhani, K.; Pungsrinont, T.; Baniahmad, A. Mechanisms of Androgen Receptor Agonist-and Antagonist-Mediated Cellular Senescence in Prostate Cancer. Cancers 2020, 12, 1833. [Google Scholar] [CrossRef] [PubMed]
- Pungsrinont, T.; Sutter, M.F.; Ertingshausen, M.C.; Lakshmana, G.; Kokal, M.; Khan, A.S.; Baniahmad, A. Senolytic Compounds Control a Distinct Fate of Androgen Receptor Agonist-and Antagonist-Induced Cellular Senescent LNCaP Prostate Cancer Cells. Cell Biosci. 2020, 10, 1–13. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Saraon, P.; Jarvi, K.; Diamandis, E.P. Molecular Alterations During Progression of Prostate Cancer to Androgen Independence. Clin. Chem. 2011, 57, 1366–1375. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Crawford, E.D.; Schellhammer, P.F.; McLeod, D.G.; Moul, J.W.; Higano, C.S.; Shore, N.; Denis, L.; Iversen, P.; Eisenberger, M.A.; Labrie, F. Androgen Receptor Targeted Treatments of Prostate Cancer: 35 Years of Progress with Antiandrogens. J. Urol. 2018, 200, 956–966. [Google Scholar] [CrossRef]
- Papaioannou, M.; Schleich, S.; Prade, I.; Degen, S.; Roell, D.; Schubert, U.; Tanner, T.; Claessens, F.; Matusch, R.; Baniahmad, A. The Natural Compound Atraric Acid Is an Antagonist of the Human Androgen Receptor Inhibiting Cellular Invasiveness and Prostate Cancer Cell Growth. J. Cell. Mol. Med. 2009, 13, 2210–2223. [Google Scholar] [CrossRef] [PubMed]
- Roediger, J.; Hessenkemper, W.; Bartsch, S.; Manvelyan, M.; Huettner, S.S.; Liehr, T.; Esmaeili, M.; Foller, S.; Petersen, I.; Grimm, M.-O.; et al. Supraphysiological Androgen Levels Induce Cellular Senescence in Human Prostate Cancer Cells through the Src-Akt Pathway. Mol. Cancer 2014, 13, 1–15. [Google Scholar] [CrossRef] [Green Version]
- Henzler, C.; Li, Y.; Yang, R.; McBride, T.; Ho, Y.; Sprenger, C.; Liu, G.; Coleman, I.; Lakely, B.; Li, R. Truncation and Constitutive Activation of the Androgen Receptor by Diverse Genomic Rearrangements in Prostate Cancer. Nat. Commun. 2016, 7, 1–12. [Google Scholar] [CrossRef]
- Kim, E.H.; Cao, D.; Mahajan, N.P.; Andriole, G.L.; Mahajan, K. Ack1–AR and AR–Hoxb13 Signaling Axes: Epigenetic Regulation of Lethal Prostate Cancers. Nar Cancer 2020, 2, zcaa018. [Google Scholar] [CrossRef] [PubMed]
- Lakshmana, G.; Baniahmad, A. Interference with the Androgen Receptor Protein Stability in Therapy—Resistant Prostate Cancer. Int. J. Cancer 2019, 144, 1775–1779. [Google Scholar] [CrossRef]
- Gupta, S.; Li, J.; Kemeny, G.; Bitting, R.L.; Beaver, J.; Somarelli, J.A.; Ware, K.E.; Gregory, S.; Armstrong, A.J. Whole Genomic Copy Number Alterations in Circulating Tumor Cells from Men with Abiraterone or Enzalutamide-Resistant Metastatic Castration-Resistant Prostate Cancer. Clin. Cancer Res. 2017, 23, 1346–1357. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Tian, X.; He, Y.; Zhou, J. Progress in Antiandrogen Design Targeting Hormone Binding Pocket to Circumvent Mutation Based Resistance. Front. Pharm. 2015, 6, 57. [Google Scholar]
- Liu, H.; Han, R.; Li, J.; Liu, H.; Zheng, L. Molecular Mechanism of R-Bicalutamide Switching from Androgen Receptor Antagonist to Agonist Induced by Amino Acid Mutations Using Molecular Dynamics Simulations and Free Energy Calculation. J. Comput. Aided Mol. Des. 2016, 30, 1189–1200. [Google Scholar] [CrossRef] [PubMed]
- Taplin, M.-E.; Bubley, G.J.; Shuster, T.D.; Frantz, M.E.; Spooner, A.E.; Ogata, G.K.; Keer, H.N.; Balk, S.P. Mutation of the Androgen-Receptor Gene in Metastatic Androgen-Independent Prostate Cancer. N. Engl. J. Med. 1995, 332, 1393–1398. [Google Scholar] [CrossRef]
- Veldscholte, J.; Berrevoets, C.A.; Brinkmann, A.O.; Grootegoed, J.A.; Mulder, E. Anti-Androgens and the Mutated Androgen Receptor of Lncap Cells: Differential Effects on Binding Affinity, Heat-Shock Protein Interaction, and Transcription Activation. Biochemistry 1992, 31, 2393–2399. [Google Scholar] [CrossRef] [PubMed]
- Liu, H.-L.; Zhong, H.-Y.; Song, T.-Q.; Li, J.-Z. A Molecular Modeling Study of the Hydroxyflutamide Resistance Mechanism Induced by Androgen Receptor Mutations. Int. J. Mol. Sci. 2017, 18, 1823. [Google Scholar] [CrossRef] [Green Version]
- Narayanan, R. Therapeutic Targeting of the Androgen Receptor (AR) and AR Variants in Prostate Cancer. Asian J. Urol. 2020. [Google Scholar] [CrossRef]
- Hirayama, Y.; Tam, T.; Jian, K.; Andersen, R.J.; Sadar, M.D. Combination Therapy with Androgen Receptor N-Terminal Domain Antagonist EPI-7170 and Enzalutamide Yields Synergistic Activity in Ar-V7-Positive Prostate Cancer. Mol. Oncol. 2020, 14, 2455–2470. [Google Scholar] [CrossRef] [PubMed]
- Cato, L.; de Tribolet-Hardy, J.; Lee, I.; Rottenberg, J.T.; Coleman, I.; Melchers, D.; Houtman, R.; Xiao, T.; Li, W.; Uo, T. ARv7 Represses Tumor-Suppressor Genes in Castration-Resistant Prostate Cancer. Cancer Cell. 2019, 35, 401–413. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Armstrong, A.J.; Halabi, S.; Luo, J.; Nanus, D.M.; Giannakakou, P.; Szmulewitz, R.Z.; Danila, D.C.; Healy, P.; Anand, M.; Rothwell, C.J.; et al. Prospective Multicenter Validation of Androgen Receptor Splice Variant 7 and Hormone Therapy Resistance in High-Risk Castration-Resistant Prostate Cancer: The Prophecy Study. J. Clin. Oncol. 2019, 37, 1120. [Google Scholar] [CrossRef]
- Zamagni, A.; Cortesi, M.; Zanoni, M.; Tesei, A. Non-Nuclear Ar Signaling in Prostate Cancer. Front. Chem. 2019, 7, 651. [Google Scholar] [CrossRef]
- Messner, E.A.; Steele, T.M.; Tsamouri, M.M.; Hejazi, N.; Gao, A.C.; Mudryj, M.; Ghosh, P.M. The Androgen Receptor in Prostate Cancer: Effect of Structure, Ligands and Spliced Variants on Therapy. Biomedicines 2020, 8, 422. [Google Scholar] [CrossRef]
- De Mol, E.; Fenwick, R.B.; Phang, C.T.; Buzon, V.; Szulc, E.; De La Fuente, A.; Escobedo, A.; García, J.; Bertoncini, C.W.; Estebanez-Perpina, E.; et al. EPI-001, a Compound Active against Castration-Resistant Prostate Cancer, Targets Transactivation Unit 5 of the Androgen Receptor. Acs Chem. Biol. 2016, 11, 2499–2505. [Google Scholar] [CrossRef] [PubMed]
- Le Moigne, R.; Zhou, H.-J.; Obst, J.K.; Banuelos, C.A.; Jian, K.; Williams, D.; Virsik, P.; Andersen, R.J.; Sadar, M.; Perabo, F. Lessons Learned from the Metastatic Castration-Resistant Prostate Cancer Phase I Trial of EPI-506, a First-Generation Androgen Receptor N-Terminal Domain Inhibitor. J. Clin. Oncol. 2019, 37, 257. [Google Scholar] [CrossRef]
- Obst, J.K.; Wang, J.; Jian, K.; Williams, D.E.; Tien, A.H.; Mawji, N.; Tam, T.; Yang, Y.C.; Andersen, R.J.; Chi, K.N.; et al. Revealing Metabolic Liabilities of Ralaniten to Enhance Novel Androgen Receptor Targeted Therapies. ACS Pharmacol. Transl. Sci. 2019, 2, 453–467. [Google Scholar] [CrossRef] [PubMed]
- Takeda, D.Y.; Spisák, S.; Seo, J.-H.; Bell, C.; O’Connor, E.; Korthauer, K.; Ribli, D.; Csabai, I.; Solymosi, N.; Szállási, Z.; et al. A Somatically Acquired Enhancer of the Androgen Receptor Is a Noncoding Driver in Advanced Prostate Cancer. Cell 2018, 174, 422–432.e13. [Google Scholar] [CrossRef] [Green Version]
- Du, M.; Tian, Y.; Tan, W.; Wang, L.; Wang, L.; Kilari, D.; Huang, C.-C.; Wang, L.; Kohli, M. Plasma Cell-Free DNA-Based Predictors of Response to Abiraterone Acetate/Prednisone and Prognostic Factors in Metastatic Castration-Resistant Prostate Cancer. Prostate Cancer Prostatic Dis. 2020, 23, 705–713. [Google Scholar] [CrossRef] [PubMed]
- Chmelar, R.; Buchanan, G.; Need, E.F.; Tilley, W.; Greenberg, N.M. Androgen Receptor Coregulators and Their Involvement in the Development and Progression of Prostate Cancer. Int. J. Cancer 2007, 120, 719–733. [Google Scholar] [CrossRef]
- Dotzlaw, H.; Papaioannou, M.; Moehren, U.; Claessens, F.; Baniahmad, A. Agonist–Antagonist Induced Coactivator and Corepressor Interplay on the Human Androgen Receptor. Mol. Cell. Endocrinol. 2003, 213, 79–85. [Google Scholar] [CrossRef] [PubMed]
- Chen, C.D.; Welsbie, D.S.; Tran, C.; Baek, S.H.; Chen, R.; Vessella, R.; Rosenfeld, M.G.; Sawyers, C.L. Molecular Determinants of Resistance to Antiandrogen Therapy. Nat. Med. 2004, 10, 33–39. [Google Scholar] [CrossRef]
- Senapati, D.; Kumari, S.; Heemers, H.V. Androgen Receptor Co-Regulation in Prostate Cancer. Asian J. Urol. 2019. [Google Scholar] [CrossRef] [PubMed]
- Augello, M.A.; Liu, D.; Deonarine, L.D.; Robinson, B.D.; Huang, D.; Stelloo, S.; Blattner, M.; Doane, A.S.; Wong, E.W.; Chen, Y.; et al. CHD1 Loss Alters AR Binding at Lineage-Specific Enhancers and Modulates Distinct Transcriptional Programs to Drive Prostate Tumorigenesis. Cancer Cell 2019, 35, 603–617. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Zhang, Z.; Zhou, C.; Li, X.; Barnes, S.D.; Deng, S.; Hoover, E.; Chen, C.-C.; Lee, Y.S.; Zhang, Y.; Wang, C.; et al. Loss of CHD1 Promotes Heterogeneous Mechanisms of Resistance to AR-Targeted Therapy Via Chromatin Dysregulation. Cancer Cell 2020, 37, 584–598. [Google Scholar] [CrossRef] [PubMed]
- Yao, J.; Chen, Y.; Nguyen, D.T.; Thompson, Z.J.; Eroshkin, A.M.; Nerlakanti, N.; Patel, A.K.; Agarwal, N.; Teer, J.K.; Dhillon, J.; et al. The Homeobox Gene, Hoxb13, Regulates a Mitotic Protein-Kinase Interaction Network in Metastatic Prostate Cancers. Sci. Rep. 2019, 9, 1–18. [Google Scholar] [CrossRef] [Green Version]
- Cheng, S.; Yang, S.; Shi, Y.; Shi, R.; Yeh, Y.; Yu, X. Neuroendocrine Prostate Cancer Has Distinctive, Non-Prostatic Hox Code That Is Represented by the Loss of Hoxb13 Expression. Sci. Rep. 2021, 11, 1–11. [Google Scholar] [CrossRef]
- Faisal, F.; Alshalalfa, M.; Davicioni, E.; Karnes, R.J.; Isaacs, W.; Lotan, T.; Schaeffer, E. Mp68-10 Hoxb13 Expression and Its Role in Prostate Cancer Progression and Neuroendocrine Differentiation. J. Urol. 2019, 201, e979. [Google Scholar] [CrossRef] [Green Version]
- Kim, Y.-R.; Oh, K.-J.; Park, R.-Y.; Xuan, N.T.; Kang, T.-W.; Kwon, D.-D.; Choi, C.; Kim, M.S.; Nam, K.I.; Ahn, K.Y.; et al. Hoxb13 Promotes Androgen Independent Growth of LNCaP Prostate Cancer Cells by the Activation of E2f Signaling. Mol. Cancer 2010, 9, 1–14. [Google Scholar] [CrossRef] [Green Version]
- Navarro, H.I.; Goldstein, A.S. Hoxb13 Mediates AR-V7 Activity in Prostate Cancer. Proc. Natl. Acad. Sci. USA 2018, 115, 6528–6529. [Google Scholar] [CrossRef] [Green Version]
- Chen, Z.; Wu, D.; Thomas-Ahner, J.M.; Lu, C.; Zhao, P.; Zhang, Q.; Geraghty, C.; Yan, P.S.; Hankey, W.; Sunkel, B.; et al. Diverse AR-V7 Cistromes in Castration-Resistant Prostate Cancer Are Governed by Hoxb13. Proc. Natl. Acad. Sci. USA 2018, 115, 6810–6815. [Google Scholar] [CrossRef] [Green Version]
- Teng, M.; Zhou, S.; Cai, C.; Lupien, M.; He, H.H. Pioneer of Prostate Cancer: Past, Present and the Future of Foxa1. Protein Cell. 2020, 1–10. [Google Scholar] [CrossRef]
- Parolia, A.; Cieslik, M.; Chu, S.-C.; Xiao, L.; Ouchi, T.; Zhang, Y.; Wang, X.; Vats, P.; Cao, X.; Pitchiaya, S.; et al. Distinct Structural Classes of Activating Foxa1 Alterations in Advanced Prostate Cancer. Nature 2019, 571, 413–418. [Google Scholar] [CrossRef]
- Büscheck, F.; Zub, M.; Heumann, A.; Hube-Magg, C.; Simon, R.; Lang, D.S.; Höflmayer, D.; Neubauer, E.; Jacobsen, F.; Hinsch, A.; et al. The Independent Prognostic Impact of the GATA2 Pioneering Factor Is Restricted to ERG-Negative Prostate Cancer. Tumour Biol. 2019, 41, 1010428318824815. [Google Scholar] [CrossRef] [Green Version]
- Vidal, S.J.; Rodriguez-Bravo, V.; Quinn, S.A.; Rodriguez-Barrueco, R.; Lujambio, A.; Williams, E.; Sun, X.; de la Iglesia-Vicente, J.; Lee, A.; Readhead, B.; et al. A Targetable GATA2-IGF2 Axis Confers Aggressiveness in Lethal Prostate Cancer. Cancer Cell 2015, 27, 223–239. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Mahajan, N.P.; Liu, Y.; Majumder, S.; Warren, M.R.; Parker, C.E.; Mohler, J.L.; Earp, H.S.; Whang, Y.E. Activated Cdc42-Associated Kinase Ack1 Promotes Prostate Cancer Progression Via Androgen Receptor Tyrosine Phosphorylation. Proc. Natl. Acad. Sci. USA 2007, 104, 8438–8443. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Liu, S.; Qi, Y.; Ge, Y.; Duplessis, T.; Rowan, B.G.; Ip, C.; Cheng, H.; Rennie, P.S.; Horikawa, I.; Lustig, A.J. Telomerase as an Important Target of Androgen Signaling Blockade for Prostate Cancer Treatment. Mol. Cancer 2010, 9, 2016–2025. [Google Scholar] [CrossRef] [Green Version]
- Czermin, B.; Melfi, R.; McCabe, D.; Seitz, V.; Imhof, A.; Pirrotta, V. Drosophila Enhancer of Zeste/Esc Complexes Have a Histone H3 Methyltransferase Activity That Marks Chromosomal Polycomb Sites. Cell 2002, 111, 185–196. [Google Scholar] [CrossRef] [Green Version]
- Liu, Q.; Wang, G.; Li, Q.; Jiang, W.; Kim, J.S.; Wang, R.; Zhu, S.; Wang, X.; Yan, L.; Yi, Y. Polycomb Group Proteins EZH2 and EED Directly Regulate Androgen Receptor in Advanced Prostate Cancer. Int. J. Cancer 2019, 145, 415–426. [Google Scholar] [CrossRef] [PubMed]
- Metzger, E.; Wissmann, M.; Yin, N.; Müller, J.M.; Schneider, R.; Peters, A.H.; Günther, T.; Buettner, R.; Schüle, R. LSD1 Demethylates Repressive Histone Marks to Promote Androgen-Receptor-Dependent Transcription. Nature 2005, 437, 436–439. [Google Scholar] [CrossRef] [PubMed]
- da Mota, S.R.; Bailey, S.; Strivens, R.A.; Hayden, A.L.; Douglas, L.R.; Duriez, P.J.; Borrello, M.T.; Benelkebir, H.; Ganesan, A.; Packham, G.; et al. LSD1 Inhibition Attenuates Androgen Receptor V7 Splice Variant Activation in Castration Resistant Prostate Cancer Models. Cancer Cell Int. 2018, 18, 1–9. [Google Scholar]
- Hwang, J.H.; Seo, J.-H.; Beshiri, M.L.; Wankowicz, S.; Liu, D.; Cheung, A.; Li, J.; Qiu, X.; Hong, A.L.; Botta, G.; et al. Creb5 Promotes Resistance to Androgen-Receptor Antagonists and Androgen Deprivation in Prostate Cancer. Cell Rep. 2019, 29, 2355–2370.e6. [Google Scholar] [CrossRef] [Green Version]
- Asim, M.; Hafeez, B.B.; Siddiqui, I.A.; Gerlach, C.; Patz, M.; Mukhtar, H.; Baniahmad, A. Ligand-Dependent Corepressor Acts as a Novel Androgen Receptor Corepressor, Inhibits Prostate Cancer Growth, and Is Functionally Inactivated by the Src Protein Kinase. J. Biol. Chem. 2011, 286, 37108–37117. [Google Scholar] [CrossRef] [Green Version]
- Tatarov, O.; Mitchell, T.J.; Seywright, M.; Leung, H.Y.; Brunton, V.G.; Edwards, J. Src Family Kinase Activity Is up-Regulated in Hormone-Refractory Prostate Cancer. Clin. Cancer Res. 2009, 15, 3540–3549. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Leung, J.K.; Sadar, M.D. Non-Genomic Actions of the Androgen Receptor in Prostate Cancer. Front. Endocrinol. 2017, 8, 2. [Google Scholar] [CrossRef] [Green Version]
- Liao, R.S.; Ma, S.; Miao, L.; Li, R.; Yin, Y.; Raj, G.V. Androgen Receptor-Mediated Non-Genomic Regulation of Prostate Cancer Cell Proliferation. Transl. Androl. Urol. 2013, 2, 187. [Google Scholar]
- Shtivelman, E.; Beer, T.M.; Evans, C.P. Molecular Pathways and Targets in Prostate Cancer. Oncotarget 2014, 5, 7217. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Toren, P.; Kim, S.; Cordonnier, T.; Crafter, C.; Davies, B.R.; Fazli, L.; Gleave, M.E.; Zoubeidi, A. Combination AZD5363 with Enzalutamide Significantly Delays Enzalutamide-Resistant Prostate Cancer in Preclinical Models. Eur. Urol. 2015, 67, 986–990. [Google Scholar] [CrossRef] [PubMed]
- Di Donato, M.; Cernera, G.; Migliaccio, A.; Castoria, G. Nerve Growth Factor Induces Proliferation and Aggressiveness in Prostate Cancer Cells. Cancers 2019, 11, 784. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Di Donato, M.; Cernera, G.; Auricchio, F.; Migliaccio, A.; Castoria, G. Cross-Talk between Androgen Receptor and Nerve Growth Factor Receptor in Prostate Cancer Cells: Implications for a New Therapeutic Approach. Cell Death Dis. 2018, 4, 1–2. [Google Scholar] [CrossRef]
- Di Donato, M.; Zamagni, A.; Giovanni, G.; Pia, G.; Barone, M.V.; Zanoni, M.; Roberta, G.; Matteo, C.; Ferdinando, A.; Antimo, M.; et al. The Androgen Receptor/Filamin a Complex as a Target in Prostate Cancer Microenvironment. Cell Death Dis. 2021, 12. [Google Scholar] [CrossRef]
- Carver, B.S.; Chapinski, C.; Wongvipat, J.; Hieronymus, H.; Chen, Y.; Chandarlapaty, S.; Arora, V.K.; Le, C.; Koutcher, J.; Scher, H.; et al. Reciprocal Feedback Regulation of Pi3k and Androgen Receptor Signaling in Pten-Deficient Prostate Cancer. Cancer Cell 2011, 19, 575–586. [Google Scholar] [CrossRef] [Green Version]
- Shorning, B.Y.; Dass, M.S.; Smalley, M.J.; Pearson, H.B. The PI3k-AKT-mTOR Pathway and Prostate Cancer: At the Crossroads of AR, Mapk, and Wnt Signaling. Int. J. Mol. Sci. 2020, 21, 4507. [Google Scholar] [CrossRef]
- Pei, H.; Li, L.; Fridley, B.L.; Jenkins, G.D.; Kalari, K.R.; Lingle, W.; Petersen, G.; Lou, Z.; Wang, L. FKBP51 Affects Cancer Cell Response to Chemotherapy by Negatively Regulating Akt. Cancer Cell 2009, 16, 259–266. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Mulholland, D.J.; Tran, L.M.; Li, Y.; Cai, H.; Morim, A.; Wang, S.; Plaisier, S.; Garraway, I.P.; Huang, J.; Graeber, T.G.; et al. Cell Autonomous Role of Pten in Regulating Castration-Resistant Prostate Cancer Growth. Cancer Cell 2011, 19, 792–804. [Google Scholar] [CrossRef] [Green Version]
- Thomas, C.; Lamoureux, F.; Crafter, C.; Davies, B.R.; Beraldi, E.; Fazli, L.; Kim, S.; Thaper, D.; Gleave, M.E.; Zoubeidi, A. Synergistic Targeting of PI3k/AKT Pathway and Androgen Receptor Axis Significantly Delays Castration-Resistant Prostate Cancer Progression in Vivo. Mol. Cancer 2013, 12, 2342–2355. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Vlaeminck-Guillem, V.; Gillet, G.; Rimokh, R. Src: Marker or Actor in Prostate Cancer Aggressiveness. Front. Oncol. 2014, 4, 222. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Liu, Y.; Karaca, M.; Zhang, Z.; Gioeli, D.; Earp, H.S.; Whang, Y.E. Dasatinib Inhibits Site-Specific Tyrosine Phosphorylation of Androgen Receptor by Ack1 and Src Kinases. Oncogene 2010, 29, 3208–3216. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Chattopadhyay, I.; Wang, J.; Qin, M.; Gao, L.; Holtz, R.; Vessella, R.L.; Leach, R.W.; Gelman, I.H. Src Promotes Castration-Recurrent Prostate Cancer through Androgen Receptor-Dependent Canonical and Non-Canonical Transcriptional Signatures. Oncotarget 2017, 8, 10324. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Zarif, J.C.; Lamb, L.E.; Schulz, V.S.; Nollet, E.A.; Miranti, C.K. Androgen Receptor Non-Nuclear Regulation of Prostate Cancer Cell Invasion Mediated by Src and Matriptase. Oncotarget 2015, 6, 6862. [Google Scholar] [CrossRef] [Green Version]
- Desai, S.J.; Ma, A.-H.; Tepper, C.G.; Chen, H.-W.; Kung, H.-J. Inappropriate Activation of the Androgen Receptor by Nonsteroids: Involvement of the Src Kinase Pathway and Its Therapeutic Implications. Cancer Res. 2006, 66, 10449–10459. [Google Scholar] [CrossRef] [Green Version]
- Chang, Y.M.; Bai, L.; Liu, S.; Yang, J.C.; Kung, H.J.; Evans, C.P. Src Family Kinase Oncogenic Potential and Pathways in Prostate Cancer as Revealed by AZD0530. Oncogene 2008, 27, 6365–6375. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Araujo, J.C.; Trudel, G.C.; Saad, F.; Armstrong, A.J.; Yu, E.Y.; Bellmunt, J.; Wilding, G.; McCaffrey, J.; Serrano, S.V.; Matveev, V.B.; et al. Docetaxel and Dasatinib or Placebo in Men with Metastatic Castration-Resistant Prostate Cancer (Ready): A Randomised, Double-Blind Phase 3 Trial. Lancet Oncol. 2013, 14, 1307–1316. [Google Scholar] [CrossRef] [Green Version]
- Giraldi, T.; Giovannelli, P.; Di Donato, M.; Castoria, G.; Migliaccio, A.; Auricchio, F. Steroid Signaling Activation and Intracellular Localization of Sex Steroid Receptors. J. Cell Commun. Signal. 2010, 4, 161–172. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Migliaccio, A.; Castoria, G.; Auricchio, F. Non-Genomic Action of Sex Steroid Hormones. In Nuclear Receptors; Springer Nature Switzerland AG: Cham, Switzerland, 2010; pp. 365–379. [Google Scholar]
- Chakraborty, G.; Patail, N.K.; Hirani, R.; Nandakumar, S.; Mazzu, Y.Z.; Yoshikawa, Y.; Atiq, M.O.; Jehane, L.; Stopsack, K.H.; Lee, G.-S.; et al. Attenuation of Src Kinase Activity Augments PARP Inhibitor-Mediated Synthetic Lethality in BRCA2-Altered Prostate Tumors. Clin. Cancer Res. 2020. [Google Scholar]
- Montgomery, R.B.; Mostaghel, E.A.; Vessella, R.; Hess, D.L.; Kalhorn, T.F.; Higano, C.S.; True, L.D.; Nelson, P.S. Maintenance of Intratumoral Androgens in Metastatic Prostate Cancer: A Mechanism for Castration-Resistant Tumor Growth. Cancer Res. 2008, 68, 4447–4454. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Chang, K.-H.; Li, R.; Kuri, B.; Lotan, Y.; Roehrborn, C.G.; Liu, J.; Vessella, R.; Nelson, P.S.; Kapur, P.; Guo, X. A Gain-of-Function Mutation in Dht Synthesis in Castration-Resistant Prostate Cancer. Cell 2013, 154, 1074–1084. [Google Scholar] [CrossRef] [Green Version]
- Saloniemi, T.; Jokela, H.; Strauss, L.; Pakarinen, P.; Poutanen, M. Thematic Review the Diversity of Sex Steroid Action: Novel Functions of Hydroxysteroid (17b) Dehydrogenases as Revealed by Genetically Modified Mouse Models. J. Endocrinol. 2012, 212, 27–40. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Chang, K.-H.; Li, R.; Papari-Zareei, M.; Watumull, L.; Zhao, Y.D.; Auchus, R.J.; Sharifi, N. Dihydrotestosterone Synthesis Bypasses Testosterone to Drive Castration-Resistant Prostate Cancer. Proc. Natl. Acad. Sci. USA 2011, 108, 13728–13733. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Maity, S.N.; Titus, M.A.; Gyftaki, R.; Wu, G.; Lu, J.-F.; Ramachandran, S.; Li-Ning-Tapia, E.M.; Logothetis, C.J.; Araujo, J.C.; Efstathiou, E. Targeting of CYP17a1 Lyase by Vt-464 Inhibits Adrenal and Intratumoral Androgen Biosynthesis and Tumor Growth of Castration Resistant Prostate Cancer. Sci. Rep. 2016, 6, 1–10. [Google Scholar] [CrossRef] [Green Version]
- Ishizaki, F.; Nishiyama, T.; Kawasaki, T.; Miyashiro, Y.; Hara, N.; Takizawa, I.; Naito, M.; Takahashi, K. Androgen Deprivation Promotes Intratumoral Synthesis of Dihydrotestosterone from Androgen Metabolites in Prostate Cancer. Sci. Rep. 2013, 3, 1–9. [Google Scholar] [CrossRef] [Green Version]
- Mostaghel, E.A. Abiraterone in the Treatment of Metastatic Castration-Resistant Prostate Cancer. Cancer Manag. Res. 2014, 6, 39. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Ryan, C.J.; Smith, M.R.; De Bono, J.S.; Molina, A.; Logothetis, C.J.; De Souza, P.; Fizazi, K.; Mainwaring, P.; Piulats, J.M.; Ng, S. Abiraterone in Metastatic Prostate Cancer without Previous Chemotherapy. N. Engl. J. Med. 2013, 368, 138–148. [Google Scholar] [CrossRef] [Green Version]
- Nguyen, H.; Yang, J.; Kung, H.-J.; Shi, X.; Tilki, D.; Lara, P.N.; White, R.D.; Gao, A.C.; Evans, C.P. Targeting Autophagy Overcomes Enzalutamide Resistance in Castration-Resistant Prostate Cancer Cells and Improves Therapeutic Response in a Xenograft Model. Oncogene 2014, 33, 4521–4530. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Wang, Q.; He, W.-Y.; Zeng, Y.-Z.; Hossain, A.; Gou, X. Inhibiting Autophagy Overcomes Docetaxel Resistance in Castration-Resistant Prostate Cancer Cells. Int. Urol. Nephrol. 2018, 50, 675–686. [Google Scholar] [CrossRef] [Green Version]
- Fulda, S.; Kögel, D. Cell Death by Autophagy: Emerging Molecular Mechanisms and Implications for Cancer Therapy. Oncogene 2015, 34, 5105–5113. [Google Scholar] [CrossRef] [PubMed]
- Nollet, E.A.; Cardo-Vila, M.; Ganguly, S.S.; Tran, J.D.; Schulz, V.V.; Cress, A.; Corey, E.; Miranti, C.K. Androgen Receptor-Induced Integrin Α6β1 and BNIP3 Promote Survival and Resistance to Pi3k Inhibitors in Castration-Resistant Prostate Cancer. Oncogene 2020, 39, 5390–5404. [Google Scholar] [CrossRef]
- Bennett, H.L.; Stockley, J.; Fleming, J.T.; Mandal, R.; O’Prey, J.; Ryan, K.M.; Robson, C.N.; Leung, H.Y. Does Androgen-Ablation Therapy (AAT) Associated Autophagy Have a Pro-Survival Effect in Lncap Human Prostate Cancer Cells? BJU Int. 2013, 111, 672–682. [Google Scholar] [CrossRef] [Green Version]
- Eberli, D.; Kranzbühler, B.; Mortezavi, A.; Sulser, T.; Salemi, S. Apalutamide in Combination with Autophagy Inhibitors Improves Treatment Effects in Prostate Cancer Cells. Urol. Oncol. Sem. Orig. Investig. 2020, 38, 683.e19–683.e26. [Google Scholar] [CrossRef] [PubMed]
- Puhr, M.; Hoefer, J.; Eigentler, A.; Ploner, C.; Handle, F.; Schaefer, G.; Kroon, J.; Leo, A.; Heidegger, I.; Eder, I.; et al. The Glucocorticoid Receptor Is a Key Player for Prostate Cancer Cell Survival and a Target for Improved Antiandrogen Therapy. Clin. Cancer Res. 2018, 24, 927–938. [Google Scholar] [CrossRef] [Green Version]
- Arora, V.K.; Schenkein, E.; Murali, R.; Subudhi, S.K.; Wongvipat, J.; Balbas, M.D.; Shah, N.; Cai, L.; Efstathiou, E.; Logothetis, C.; et al. Glucocorticoid Receptor Confers Resistance to Antiandrogens by Bypassing Androgen Receptor Blockade. Cell 2013, 155, 1309–1322. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Shah, N.; Wang, P.; Wongvipat, J.; Karthaus, W.R.; Abida, W.; Armenia, J.; Rockowitz, S.; Drier, Y.; Bernstein, B.E.; Long, H.W. Regulation of the Glucocorticoid Receptor Via a BET-Dependent Enhancer Drives Antiandrogen Resistance in Prostate Cancer. Elife 2017, 6, e27861. [Google Scholar] [CrossRef]
- Sahu, B.; Laakso, M.; Pihlajamaa, P.; Ovaska, K.; Sinielnikov, I.; Hautaniemi, S.; Jänne, O.A. FOXA1 Specifies Unique Androgen and Glucocorticoid Receptor Binding Events in Prostate Cancer Cells. Cancer Res. 2013, 73, 1570–1580. [Google Scholar] [CrossRef] [Green Version]
- Claessens, F.; Joniau, S.; Helsen, C. Comparing the Rules of Engagement of Androgen and Glucocorticoid Receptors. Cell. Mol. Life Sci. 2017, 74, 2217–2228. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Borschiwer, M.; Bothe, M.; Kibar, G.; Fuchs, A.; Schöne, S.; Prekovic, S.; Peralta, I.M.; Chung, H.-R.; Zwart, W.H.; Helsen, C.; et al. Androgen and Glucocorticoid Receptor Direct Distinct Transcriptional Programs by Receptor-Specific and Shared DNA Binding Sites. Biorxiv 2020. [Google Scholar]
- Smith, R.; Liu, M.; Liby, T.; Bayani, N.; Bucher, E.; Chiotti, K.; Derrick, D.; Chauchereau, A.; Heiser, L.; Alumkal, J. Enzalutamide Response in a Panel of Prostate Cancer Cell Lines Reveals a Role for Glucocorticoid Receptor in Enzalutamide Resistant Disease. Sci. Rep. 2020, 10, 1–13. [Google Scholar] [CrossRef] [PubMed]
- Chen, X.; Chen, F.; Ren, Y.; Weng, G.; Keng, P.C.; Chen, Y.; Lee, S.O. Glucocorticoid Receptor Upregulation Increases Radioresistance and Triggers Androgen Independence of Prostate Cancer. Prostate 2019, 79, 1414–1426. [Google Scholar] [CrossRef]
- Niu, Y.; Guo, C.; Wen, S.; Tian, J.; Luo, J.; Wang, K.; Tian, H.; Yeh, S.; Chang, C. ADT with Antiandrogens in Prostate Cancer Induces Adverse Effect of Increasing Resistance, Neuroendocrine Differentiation and Tumor Metastasis. Cancer Lett. 2018, 439, 47–55. [Google Scholar] [CrossRef]
- Hirano, D.; Okada, Y.; Minei, S.; Takimoto, Y.; Nemoto, N. Neuroendocrine Differentiation in Hormone Refractory Prostate Cancer Following Androgen Deprivation Therapy. Eur. Urol. 2004, 45, 586–592. [Google Scholar] [CrossRef]
- Lee, J.K.; Phillips, J.W.; Smith, B.A.; Park, J.W.; Stoyanova, T.; McCaffrey, E.F.; Baertsch, R.; Sokolov, A.; Meyerowitz, J.G.; Mathis, C.; et al. N-Myc Drives Neuroendocrine Prostate Cancer Initiated from Human Prostate Epithelial Cells. Cancer Cell 2016, 29, 536–547. [Google Scholar] [CrossRef] [Green Version]
- Dardenne, E.; Beltran, H.; Benelli, M.; Gayvert, K.; Berger, A.; Puca, L.; Cyrta, J.; Sboner, A.; Noorzad, Z.; MacDonald, T.; et al. N-Myc Induces an EZH2-Mediated Transcriptional Program Driving Neuroendocrine Prostate Cancer. Cancer Cell 2016, 30, 563–577. [Google Scholar] [CrossRef] [Green Version]
- Yin, Y.; Xu, L.; Chang, Y.; Zeng, T.; Chen, X.; Wang, A.; Groth, J.; Foo, W.-C.; Liang, C.; Hu, H. N-Myc Promotes Therapeutic Resistance Development of Neuroendocrine Prostate Cancer by Differentially Regulating Mir-421/ATM Pathway. Mol. Cancer 2019, 18, 1–13. [Google Scholar]
- Gupta, K.; Gupta, S. Neuroendocrine Differentiation in Prostate Cancer: Key Epigenetic Players. Transl. Cancer Res. 2017, 6, S104. [Google Scholar] [CrossRef]
- Krijnen, J.; Janssen, P.; de Winter, J.R.; Van Krimpen, H.; Schröder, F.; van der Kwast, T.H. Do Neuroendocrine Cells in Human Prostate Cancer Express Androgen Receptor? Histochemistry 1993, 100, 393–398. [Google Scholar] [CrossRef] [Green Version]
- Davies, A.; Zoubeidi, A.; Selth, L.A. The Epigenetic and Transcriptional Landscape of Neuroendocrine Prostate Cancer. Endocr. Relat. Cancer 2020, 27, R35–R50. [Google Scholar] [CrossRef] [PubMed]
- Aggarwal, R.; Huang, J.; Alumkal, J.J.; Zhang, L.; Feng, F.Y.; Thomas, G.V.; Weinstein, A.S.; Friedl, V.; Zhang, C.; Witte, O.N. Clinical and Genomic Characterization of Treatment-Emergent Small-Cell Neuroendocrine Prostate Cancer: A Multi-Institutional Prospective Study. J. Clin. Oncol. 2018, 36, 2492. [Google Scholar] [CrossRef]
- Rotinen, M.; You, S.; Yang, J.; Coetzee, S.G.; Reis-Sobreiro, M.; Huang, W.-C.; Huang, F.; Pan, X.; Yáñez, A.; Hazelett, D.J.; et al. ONECUT2 Is a Targetable Master Regulator of Lethal Prostate Cancer That Suppresses the Androgen Axis. Nat. Med. 2018, 24, 1887–1898. [Google Scholar] [CrossRef] [PubMed]
- Yamada, Y.; Beltran, H. Clinical and Biological Features of Neuroendocrine Prostate Cancer. Curr. Oncol. Rep. 2021, 23, 1–10. [Google Scholar] [CrossRef]
- Ostano, P.; Mello-Grand, M.; Sesia, D.; Gregnanin, I.; Peraldo-Neia, C.; Guana, F.; Jachetti, E.; Farsetti, A.; Chiorino, G. Gene Expression Signature Predictive of Neuroendocrine Transformation in Prostate Adenocarcinoma. Int. J. Mol. Sci. 2020, 21, 1078. [Google Scholar] [CrossRef] [Green Version]
- Alimirah, F.; Panchanathan, R.; Chen, J.; Zhang, X.; Ho, S.-M.; Choubey, D. Expression of Androgen Receptor Is Negatively Regulated by P53. Neoplasia 2007, 9, 1152–1159. [Google Scholar] [CrossRef] [Green Version]
- Hientz, K.; Mohr, A.; Bhakta-Guha, D.; Efferth, T. The Role of P53 in Cancer Drug Resistance and Targeted Chemotherapy. Oncotarget 2017, 8, 8921. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Debelec-Butuner, B.; Kotmakci, M.; Oner, E.; Ozduman, G.; Kantarci, A.G. Nutlin3a-Loaded Nanoparticles Show Enhanced Apoptotic Activity on Prostate Cancer Cells. Mol. Biotechnol. 2019, 61, 489–497. [Google Scholar] [CrossRef]
- Feng, F.Y.; Zhang, Y.; Kothari, V.; Evans, J.R.; Jackson, W.C.; Chen, W.; Johnson, S.B.; Luczak, C.; Wang, S.; Hamstra, D.A. Mdm2 Inhibition Sensitizes Prostate Cancer Cells to Androgen Ablation and Radiotherapy in a p53-Dependent Manner. Neoplasia 2016, 18, 213–222. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Ingersoll, M.A.; Chou, Y.-W.; Lin, J.S.; Yuan, T.-C.; Miller, D.R.; Xie, Y.; Tu, Y.; Oberley-Deegan, R.E.; Batra, S.K.; Lin, M.-F. P66shc Regulates Migration of Castration-Resistant Prostate Cancer Cells. Cell. Signal. 2018, 46, 1–14. [Google Scholar] [CrossRef]
- Miller, D.R.; Ingersoll, M.A.; Chatterjee, A.; Baker, B.; Shrishrimal, S.; Kosmacek, E.A.; Zhu, Y.; Cheng, P.-W.; Oberley-Deegan, R.E.; Lin, M.-F. P66shc Protein through a Redox Mechanism Enhances the Progression of Prostate Cancer Cells Towards Castration-Resistance. Free Radic. Biol. Med. 2019, 139, 24–34. [Google Scholar] [CrossRef] [PubMed]
- Li, F.; Mahato, R.I. Micrornas and Drug Resistance in Prostate Cancers. Mol. Pharm. 2014, 11, 2539–2552. [Google Scholar] [CrossRef]
- Wang, S.; Li, M.-Y.; Liu, Y.; Vlantis, A.C.; Chan, J.Y.; Xue, L.; Hu, B.-G.; Yang, S.; Chen, M.-X.; Zhou, S. The Role of Microrna in Cisplatin Resistance or Sensitivity. Expert Opin. Targets 2020, 24, 885–897. [Google Scholar] [CrossRef] [PubMed]
- Prensner, J.R.; Chen, W.; Iyer, M.K.; Cao, Q.; Ma, T.; Han, S.; Sahu, A.; Malik, R.; Wilder-Romans, K.; Navone, N. PCAT-1, a Long Noncoding RNA, Regulates BRCA2 and Controls Homologous Recombination in Cancer. Cancer Res. 2014, 74, 1651–1660. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Xiong, T.; Li, J.; Chen, F.; Zhang, F. Pcat-1: A Novel Oncogenic Long Non-Coding Rna in Human Cancers. Int. J. Biol. Sci. 2019, 15, 847. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Hagman, Z.; Haflidadottir, B.; Ceder, J.; Larne, O.; Bjartell, A.; Lilja, H.; Edsjö, A.; Ceder, Y. Mir-205 Negatively Regulates the Androgen Receptor and Is Associated with Adverse Outcome of Prostate Cancer Patients. Br. J. Cancer 2013, 108, 1668–1676. [Google Scholar] [CrossRef] [PubMed]
- Lin, P.-C.; Chiu, Y.-L.; Banerjee, S.; Park, K.; Mosquera, J.M.; Giannopoulou, E.; Alves, P.; Tewari, A.K.; Gerstein, M.B.; Beltran, H.; et al. Epigenetic Repression of Mir-31 Disrupts Androgen Receptor Homeostasis and Contributes to Prostate Cancer Progression. Cancer Res. 2013, 73, 1232–1244. [Google Scholar] [CrossRef] [Green Version]
- Bhatnagar, N.; Li, X.; Padi, S.K.; Zhang, Q.; Tang, M.; Guo, B. Downregulation of Mir-205 and Mir-31 Confers Resistance to Chemotherapy-Induced Apoptosis in Prostate Cancer Cells. Cell Death Dis. 2010, 1, e105. [Google Scholar] [CrossRef] [Green Version]
- Chen, J.; Wang, F.; Xu, H.; Xu, L.; Chen, D.; Wang, J.; Huang, S.; Wen, Y.; Fang, L. Long Non-Coding RNA Snhg1 Regulates the Wnt/Β-Catenin and PI3k/AKT/mTOR Signaling Pathways Via Ezh2 to Affect the Proliferation, Apoptosis, and Autophagy of Prostate Cancer Cell. Front. Oncol. 2020, 10. [Google Scholar] [CrossRef] [PubMed]
- Rossi, J.F.; Lu, Z.Y.; Jourdan, M.; Klein, B. Interleukin-6 as a Therapeutic Target. Clin. Cancer Res. 2015, 21, 1248–1257. [Google Scholar] [CrossRef] [Green Version]
- Culig, Z. Interleukin-6 Function and Targeting in Prostate Cancer; Tumor Microenvironment: The Role of Interleukins–Part B; Springer Nature Switzerland AG: Cham, Switzerland, 2021. [Google Scholar]
- Wang, S.; Yang, Y.; Cao, Y.-D.; Tang, X.-X.; Du, P. Androgen Downregulation of Mir-760 Promotes Prostate Cancer Cell Growth by Regulating Il6. Asian J. Androl. 2021, 23, 85. [Google Scholar]
- Bishop, J.L.; Thaper, D.; Zoubeidi, A. The Multifaceted Roles of STAT3 Signaling in the Progression of Prostate Cancer. Cancers 2014, 6, 829–859. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Hua, Y.; Azeem, W.; Shen, Y.; Zhang, S.; Olsen, J.R.; Øyan, A.M.; Ke, X.; Zhang, W.; Kalland, K.H. Dual Androgen Receptor (AR) and STAT3 Inhibition by a Compound Targeting the AR Amino-Terminal Domain. Pharmacol. Res. Perspect. 2018, 6, e00437. [Google Scholar] [CrossRef] [Green Version]
- Eichten, A.; Su, J.; Adler, A.P.; Zhang, L.; Ioffe, E.; Parveen, A.A.; Yancopoulos, G.D.; Rudge, J.; Lowy, I.; Lin, H.C.; et al. Resistance to Anti-VEGF Therapy Mediated by Autocrine Il6/STAT3 Signaling and Overcome by Il6 Blockade. Cancer Res. 2016, 76, 2327–2339. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Handle, F.; Puhr, M.; Schaefer, G.; Lorito, N.; Hoefer, J.; Gruber, M.; Guggenberger, F.; Santer, F.R.; Marques, R.B.; van Weerden, W.M. The STAT3 Inhibitor Galiellalactone Reduces Il6-Mediated Ar Activity in Benign and Malignant Prostate Models. Mol. Cancer 2018, 17, 2722–2731. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Liu, C.; Lou, W.; Zhu, Y.; Nadiminty, N.; Schwartz, C.T.; Evans, C.P.; Gao, A.C. Niclosamide Inhibits Androgen Receptor Variants Expression and Overcomes Enzalutamide Resistance in Castration-Resistant Prostate Cancer. Clin. Cancer Res. 2014, 20, 3198–3210. [Google Scholar] [CrossRef] [Green Version]
- Fizazi, K.; De Bono, J.; Flechon, A.; Heidenreich, A.; Voog, E.; Davis, N.; Qi, M.; Bandekar, R.; Vermeulen, J.; Cornfeld, M. Randomised Phase II Study of Siltuximab (Cnto 328), an Anti-Il-6 Monoclonal Antibody, in Combination with Mitoxantrone/Prednisone Versus Mitoxantrone/Prednisone Alone in Metastatic Castration-Resistant Prostate Cancer. Eur. J. Cancer 2012, 48, 85–93. [Google Scholar] [CrossRef]
- Karkera, J.; Steiner, H.; Li, W.; Skradski, V.; Moser, P.L.; Riethdorf, S.; Reddy, M.; Puchalski, T.; Safer, K.; Prabhakar, U. The Anti-Interleukin-6 Antibody Siltuximab Down-Regulates Genes Implicated in Tumorigenesis in Prostate Cancer Patients from a Phase I Study. Prostate 2011, 71, 1455–1465. [Google Scholar] [CrossRef] [PubMed]
- Pal, S.K.; Moreira, D.; Won, H.; White, S.W.; Duttagupta, P.; Lucia, M.; Jones, J.; Hsu, J.; Kortylewski, M. Reduced T-Cell Numbers and Elevated Levels of Immunomodulatory Cytokines in Metastatic Prostate Cancer Patients De Novo Resistant to Abiraterone and/or Enzalutamide Therapy. Int. J. Mol. Sci. 2019, 20, 1831. [Google Scholar] [CrossRef] [Green Version]
- Dorff, T.B.; Goldman, B.; Pinski, J.K.; Mack, P.C.; Lara, P.N.; Van Veldhuizen, P.J.; Quinn, D.I.; Vogelzang, N.J.; Thompson, I.M.; Hussain, M.H. Clinical and Correlative Results of Swog S0354: A Phase II Trial of Cnto328 (Siltuximab), a Monoclonal Antibody against Interleukin-6, in Chemotherapy-Pretreated Patients with Castration-Resistant Prostate Cancer. Clin. Cancer Res. 2010, 16, 3028–3034. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Lu, Z.Y.; Brochier, J.; Wijdenes, J.; Brailly, H.; Bataille, R.; Klein, B. High Amounts of Circulating Interleukin (IL)-6 in the Form of Monomeric Immune Complexes During Anti-IL-6 Therapy. Towards a New Methodology for Measuring Overall Cytokine Production in Human in Vivo. Eur. J. Immunol. 1992, 22, 2819–2824. [Google Scholar] [CrossRef]
- Baritaki, S.; Chapman, A.; Yeung, K.; Spandidos, D.; Palladino, M.; Bonavida, B. Inhibition of Epithelial to Mesenchymal Transition in Metastatic Prostate Cancer Cells by the Novel Proteasome Inhibitor, NPI-0052: Pivotal Roles of Snail Repression and Rkip Induction. Oncogene 2009, 28, 3573–3585. [Google Scholar] [CrossRef] [Green Version]
- Montanari, M.; Rossetti, S.; Cavaliere, C.; D’Aniello, C.; Malzone, M.G.; Vanacore, D.; Di Franco, R.; La Mantia, E.; Iovane, G.; Piscitelli, R. Epithelial-Mesenchymal Transition in Prostate Cancer: An Overview. Oncotarget 2017, 8, 35376. [Google Scholar] [CrossRef] [Green Version]
- Kalluri, R.; Weinberg, R.A. The Basics of Epithelial-Mesenchymal Transition. J. Clin. Investig. 2010, 120, 1786–1789. [Google Scholar] [CrossRef] [Green Version]
- Liu, Q.; Tong, D.; Liu, G.; Xu, J.; Do, K.; Geary, K.; Zhang, D.; Zhang, J.; Zhang, Y.; Li, Y. Metformin Reverses Prostate Cancer Resistance to Enzalutamide by Targeting Tgf-Β 1/Stat3 Axis-Regulated Emt. Cell Death Dis. 2017, 8, e3007. [Google Scholar] [CrossRef]
- Schroeder, A.; Herrmann, A.; Cherryholmes, G.; Kowolik, C.; Buettner, R.; Pal, S.; Yu, H.; Müller-Newen, G.; Jove, R. Loss of Androgen Receptor Expression Promotes a Stem-Like Cell Phenotype in Prostate Cancer through Stat3 Signaling. Cancer Res. 2014, 74, 1227–1237. [Google Scholar] [CrossRef] [Green Version]
- Traish, A.; Morgentaler, A. Epidermal Growth Factor Receptor Expression Escapes Androgen Regulation in Prostate Cancer: A Potential Molecular Switch for Tumour Growth. Br. J. Cancer 2009, 101, 1949–1956. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Day, K.C.; Hiles, G.L.; Kozminsky, M.; Dawsey, S.J.; Paul, A.; Broses, L.J.; Shah, R.; Kunja, L.P.; Hall, C.; Palanisamy, N. Her2 and EGFR Overexpression Support Metastatic Progression of Prostate Cancer to Bone. Cancer Res. 2017, 77, 74–85. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Hour, T.-C.; Chung, S.-D.; Kang, W.-Y.; Lin, Y.-C.; Chuang, S.-J.; Huang, A.-M.; Wu, W.-J.; Huang, S.-P.; Huang, C.-Y.; Pu, Y.-S. EGFR Mediates Docetaxel Resistance in Human Castration-Resistant Prostate Cancer through the AKT-Dependent Expression of ABCD1 (Mdr1). Arch. Toxicol. 2015, 89, 591–605. [Google Scholar] [CrossRef] [PubMed]
- Liao, Y.; Guo, Z.; Xia, X.; Liu, Y.; Huang, C.; Jiang, L.; Wang, X.; Liu, J.; Huang, H. Inhibition of EGFR Signaling with Spautin-1 Represents a Novel Therapeutics for Prostate Cancer. J. Exp. Clin. Cancer Res. 2019, 38, 1–16. [Google Scholar] [CrossRef] [PubMed]
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. |
© 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
Share and Cite
Ehsani, M.; David, F.O.; Baniahmad, A. Androgen Receptor-Dependent Mechanisms Mediating Drug Resistance in Prostate Cancer. Cancers 2021, 13, 1534. https://doi.org/10.3390/cancers13071534
Ehsani M, David FO, Baniahmad A. Androgen Receptor-Dependent Mechanisms Mediating Drug Resistance in Prostate Cancer. Cancers. 2021; 13(7):1534. https://doi.org/10.3390/cancers13071534
Chicago/Turabian StyleEhsani, Marzieh, Faith Oluwakemi David, and Aria Baniahmad. 2021. "Androgen Receptor-Dependent Mechanisms Mediating Drug Resistance in Prostate Cancer" Cancers 13, no. 7: 1534. https://doi.org/10.3390/cancers13071534