CYR61 promotes metastasis of prostate cancer cells through the p-AKT and AR signaling pathways

Read the full article See related articles

Listed in

This article is not in any list yet, why not save it to one of your lists.
Log in to save this article

Abstract

Background Previous studies have shown that the cysteine-rich angiogenic inducer 61 (CYR61) contributes to prostate cancer (PCa) cell growth and survival, but its role in PCa progression is unknown. As CYR61 contains an insulin-like growth factor-binding protein domain, and insulin-like growth factor-1 (IGF1) signaling is associated with PCa progression and metastases, we evaluated their molecular interplay. Methods We performed siRNA knockdown of PCa cell lines including prostate carcinoma 3 (PC3) and lymph node carcinoma of the prostate (LNCaP) to investigate the role of CYR61 in PCa progression. Cells were evaluated for viability, proliferation, clonogenicity, aggregation, wound healing, and transwell migration. To examine the underlying mechanisms associated with CYR61 signaling, we assessed the activation of the PI3/AKT and MAPK pathways. Monolayer cultures treated with recombinant IGF1 at different time points were analyzed for CYR61 expression by in-cell western assays. Results Knockdown of CYR61 using siRNA significantly reduced cell proliferation, viability, prostasphere and colony formation, metabolic activity, and migration of PC3 and LNCaP cells, when compared with cells receiving scrambled control siRNA. In PC3 and LNCaP cells, CYR61 silencing inhibited the activation of the PI3/AKT pathway but did not impact the activity of MAPK pathways. In LNCaP cells, CYR61 silencing decreased levels of the androgen receptor (AR) splice variant AR-V7. We also found that recombinant IGF1 induced protein expression of CYR61 in a time-dependent manner in PC3 and LNCaP cells. Conclusion CYR61 expression was induced by recombinant IGF1, and knockdown of CYR61 decreased the capacity of metastatic PCa cells to proliferate. These results underscore the therapeutic potential of CYR61 inhibition in reducing the proliferation and metastatic capabilities of PCa cells.

Article activity feed