YAP1 Regulates the YAP1/AR/PSA Axis Through Autophagy in Castration-Resistant Prostate Cancer and Mediates T-Cell Immune and Inflammatory Cytokine Infiltration

Overview

Journal Biomedicines

Specialty Biomedical Engineering

Date 2024 Mar 28

PMID 38540274

Authors

Youzhi Wang

Ning Wu

Junbo Li

Diansheng Zhou

Jiaming Liang

Qian Cao

Zhaokai Guan

Yangyang Xu

Ning Jiang

Affiliations

Soon will be listed here.

Abstract

The emergence of castration-resistant prostate cancer (CRPC) following androgen deprivation therapy (ADT) is associated with increased malignancy and limited treatment options. This study aims to investigate potential connections between immune cell infiltration and inflammatory cytokines with the YAP1/AR/PSA axis by exploring their interactions with autophagy. Our research reveals heightened levels of Yes-associated protein 1 (YAP1) expression in CRPC tissues compared with tissues from androgen-dependent prostate cancer (ADPC) and benign prostate hyperplasia (BPH). Additionally, a correlation was observed between YAP1 and PSA expressions in CRPC tissues, suggesting that YAP1 may exert a regulatory influence on PSA expression within CRPC. Enhanced YAP1 expression in C4-2 cells resulted in the upregulation of androgen receptor (AR) nuclear translocation and intracellular prostate-specific antigen (PSA) levels. Conversely, the suppression of YAP1 led to a decrease in PSA expression, suggesting that YAP1 may positively regulate the PSA in castration-resistant prostate cancer (CRPC) by facilitating AR nuclear import. The modulation of the autophagy activity exerts a significant impact on the expression levels of YAP1, the AR, and the PSA. Moreover, recent advancements in immunity and inflammation studies present promising avenues for potential therapies targeting prostate cancer (PC).

References

Marzagalli M, Ebelt N, Manuel E . Unraveling the crosstalk between melanoma and immune cells in the tumor microenvironment. Semin Cancer Biol. 2019; 59:236-250. DOI: 10.1016/j.semcancer.2019.08.002. View

Li Q, Wang M, Hu Y, Zhao E, Li J, Ren L . MYBL2 disrupts the Hippo-YAP pathway and confers castration resistance and metastatic potential in prostate cancer. Theranostics. 2021; 11(12):5794-5812. PMC: 8058714. DOI: 10.7150/thno.56604. View

Gillessen S, Bossi A, Davis I, de Bono J, Fizazi K, James N . Management of Patients with Advanced Prostate Cancer. Part I: Intermediate-/High-risk and Locally Advanced Disease, Biochemical Relapse, and Side Effects of Hormonal Treatment: Report of the Advanced Prostate Cancer Consensus Conference 2022. Eur Urol. 2022; 83(3):267-293. PMC: 7614721. DOI: 10.1016/j.eururo.2022.11.002. View

Small E, Saad F, Chowdhury S, Oudard S, Hadaschik B, Graff J . Apalutamide and overall survival in non-metastatic castration-resistant prostate cancer. Ann Oncol. 2019; 30(11):1813-1820. PMC: 6927320. DOI: 10.1093/annonc/mdz397. View

Baran K, Wasko J, Kryczka J, Boncela J, Jablonski S, Kolesinska B . The Comparison of Serum Exosome Protein Profile in Diagnosis of NSCLC Patients. Int J Mol Sci. 2023; 24(18). PMC: 10650331. DOI: 10.3390/ijms241813669. View

Xiao L, Parolia A, Qiao Y, Bawa P, Eyunni S, Mannan R . Targeting SWI/SNF ATPases in enhancer-addicted prostate cancer. Nature. 2021; 601(7893):434-439. PMC: 8770127. DOI: 10.1038/s41586-021-04246-z. View

Lu X, Horner J, Paul E, Shang X, Troncoso P, Deng P . Effective combinatorial immunotherapy for castration-resistant prostate cancer. Nature. 2017; 543(7647):728-732. PMC: 5374023. DOI: 10.1038/nature21676. View

Xue J, Shi Z, Zou J, Li X . Inhibition of PI3K/AKT/mTOR signaling pathway promotes autophagy of articular chondrocytes and attenuates inflammatory response in rats with osteoarthritis. Biomed Pharmacother. 2017; 89:1252-1261. DOI: 10.1016/j.biopha.2017.01.130. View

Wu N, Wang Y, Wang K, Zhong B, Liao Y, Liang J . Cathepsin K regulates the tumor growth and metastasis by IL-17/CTSK/EMT axis and mediates M2 macrophage polarization in castration-resistant prostate cancer. Cell Death Dis. 2022; 13(9):813. PMC: 9499936. DOI: 10.1038/s41419-022-05215-8. View

10.

Bainbridge A, Walker S, Smith J, Patterson K, Dutt A, Min Ng Y . IKBKE activity enhances AR levels in advanced prostate cancer via modulation of the Hippo pathway. Nucleic Acids Res. 2020; 48(10):5366-5382. PMC: 7261174. DOI: 10.1093/nar/gkaa271. View

11.

Pala L, De Pas T, Conforti F . Boosting anticancer immunotherapy through androgen receptor blockade. Cancer Cell. 2022; 40(5):455-457. DOI: 10.1016/j.ccell.2022.04.007. View

12.

Liang J, Liao Y, Wang P, Yang K, Wang Y, Wang K . Ferroptosis landscape in prostate cancer from molecular and metabolic perspective. Cell Death Discov. 2023; 9(1):128. PMC: 10105735. DOI: 10.1038/s41420-023-01430-0. View

13.

Wang X, Jiang Z, Xu C, Meng W, Liu P, Zhang Y . Andrographolide suppresses non-small-cell lung cancer progression through induction of autophagy and antitumor immune response. Pharmacol Res. 2022; 179:106198. DOI: 10.1016/j.phrs.2022.106198. View

14.

Sandhu S, Moore C, Chiong E, Beltran H, Bristow R, Williams S . Prostate cancer. Lancet. 2021; 398(10305):1075-1090. DOI: 10.1016/S0140-6736(21)00950-8. View

15.

Wang L, Luo J, Li B, Tian X, Chen L, Huang Y . Integrin-YAP/TAZ-JNK cascade mediates atheroprotective effect of unidirectional shear flow. Nature. 2016; 540(7634):579-582. DOI: 10.1038/nature20602. View

16.

Zhang L, Yang S, Chen X, Stauffer S, Yu F, Lele S . The hippo pathway effector YAP regulates motility, invasion, and castration-resistant growth of prostate cancer cells. Mol Cell Biol. 2015; 35(8):1350-62. PMC: 4372700. DOI: 10.1128/MCB.00102-15. View

17.

Zhang W, Yan Y, Wu Y, Yang H, Zhu P, Yan F . Medicinal herbs for the treatment of anxiety: A systematic review and network meta-analysis. Pharmacol Res. 2022; 179:106204. DOI: 10.1016/j.phrs.2022.106204. View

18.

Chen Q, Zhang M, Li Y, Xu D, Wang Y, Song A . CXCR7 Mediates Neural Progenitor Cells Migration to CXCL12 Independent of CXCR4. Stem Cells. 2015; 33(8):2574-85. PMC: 4867224. DOI: 10.1002/stem.2022. View

19.

Hu F, Song D, Yan Y, Huang C, Shen C, Lan J . IL-6 regulates autophagy and chemotherapy resistance by promoting BECN1 phosphorylation. Nat Commun. 2021; 12(1):3651. PMC: 8206314. DOI: 10.1038/s41467-021-23923-1. View

20.

Alonso-Perez J, Carrasco-Rozas A, Borrell-Pages M, Fernandez-Simon E, Pinol-Jurado P, Badimon L . Nintedanib Reduces Muscle Fibrosis and Improves Muscle Function of the Alpha-Sarcoglycan-Deficient Mice. Biomedicines. 2022; 10(10). PMC: 9599168. DOI: 10.3390/biomedicines10102629. View