<b>Introduction</b>: The androgen receptor (AR) regulates immune-related epithelial-to-mesenchymal transition (EMT), and prostate cancer (PCa) metastasis.
Metastases with AR amplification showed high AR and AR-V7 mRNA levels, increased nuclear AR immunostaining, and co-amplification of genes such as YIPF6 in the AR proximity at Xq12.
Androgen receptor (AR) signaling is a critical survival pathway for prostate cancer cells, and androgen-deprivation therapy (ADT) remains the principal treatment for patients with locally advanced and metastatic disease.
Androgen receptor (AR) signaling is a critical pathway for prostate cancer cells, and androgen-deprivation therapy (ADT) remains the principal treatment for patients with locally advanced and metastatic disease.
Androgen receptor (AR) signaling is a critical survival pathway for prostate cancer cells, and androgen-deprivation therapy (ADT) remains the principal treatment for patients with locally advanced and metastatic disease.
Androgen receptor (AR) is a validated drug target for prostate cancer based on its role in proliferation, survival, and metastases of prostate cancer cells.
Androgen receptor (AR) signaling is a key driver of prostate cancer, and androgen-deprivation therapy (ADT) is a standard treatment for patients with advanced and metastatic disease.
A second tumor-suppressive lncRNA PCAT29, located 20 kb downstream of DRAIC, is regulated identically by AR and FOXA1 and also suppresses cellular migration and metastasis.
Accordingly, infiltration of CD3<sup>+</sup> and CD68<sup>+</sup> cells was lower in AR-driven than in non-AR-driven metastases, and tumor cell HLA class I ABC immunoreactivity was inversely correlated with nuclear AR immunoreactivity.
After examination of medical records of 100 patients diagnosed with prostate cancer, it was found that the AR was expressed in both cellular compartments of cancer cells in 81% of cases when cancer was found to have metastasized outside the prostate.
All other correlations of AR expression in primary tumors and metastases with quantitative (age, prostate cancer volume, number of metastases) or categorical (tumor stage, Gleason score of the primary tumor and metastases) tumor characteristics or with survival were insignificant.
Although both luminal-like subtypes were associated with increased androgen receptor expression and signaling, only luminal B prostate cancers were significantly associated with postoperative response to androgen deprivation therapy (ADT) in a subset analysis in our retrospective cohorts (n = 315) matching patients based on clinicopathologic variables (luminal B 10-year metastasis: treated, 33% vs untreated, 55%; nonluminal B 10-year metastasis: treated, 37% vs untreated, 21%; P = .006 for interaction).
Among the six ECM genes, SPP1 was identified as the key hub signature for PCa metastasis and drug resistance development; we found that both protein and mRNA expression levels of SPP1 were remarkably up-regulated in mCRPC compared with HSPC in organoid models and could regulate the androgen receptor signaling pathway.
As PCa is hormone dependent, blockade of the androgen receptor (AR) signaling is an effective therapeutic strategy for men with advanced metastatic disease.
Body mass index (P = .023) and DACH1 (P = .034) were correlated with MBC prognosis, whereas the expression of AR (P = .049), SIX1 (P = .048), surgery (P < .001), and chemotherapy (P = .001) were important for FBC in addition to already known factors: tumor size and location, TNM stage (lymph nodes and organ metastasis), radiotherapy, and ER and human epidermalgrowth factor receptor-2 (HER2) expression.
Cancer cells maintain androgen receptor-regulated cytoplasmic TMPRSS2 expression, which facilitates EMT invasion and metastasis in model systems through hepatocyte growth factor and c-MET signaling.
Coexpression analyses showed an increase of the double-positive (AR<sup>+</sup> /ARv7<sup>+</sup> ) population in metastases compared to benign, and an increase of the double-negative population in PRCA samples compared to benign.
Combining different clinical agents to target multiple pathways in prostate cancer cells, including androgen receptor (AR) signaling, is potentially an effective strategy to improve outcomes for men with metastatic disease.
Copy number variability and dysregulation of specific pathways including androgen receptor signaling, PTEN/PAKT and TGF-β continue to play an important role in invasion and metastasis.