Targeting the androgen receptor with siRNA promotes prostate cancer metastasis through enhanced macrophage recruitment via CCL2/CCR2-induced STAT3 activation.

ABSTRACT: Increased CCL2 expression in prostate cancer (PCa) cells enhanced metastasis via macrophage recruitment. However, its linkage to androgen receptor (AR)-mediated PCa progression remains unclear. Here, we identified a previously unrecognized regulation: targeting AR with siRNA in PCa cells increased macrophage recruitment via CCL2 up-regulation, which might then result in enhancing PCa invasiveness. Molecular mechanism dissection revealed that targeting PCa AR with siRNA promoted PCa cell migration/invasion via CCL2-dependent STAT3 activation and epithelial-mesenchymal transition (EMT) pathways. Importantly, pharmacologic interruption of the CCL2/CCR2-STAT3 axis suppressed EMT and PCa cell migration, providing a new mechanism linking CCL2 and EMT. Simultaneously targeting PCa AR with siRNA a

SUBMITTER: Izumi K 

PROVIDER: S-EPMC3799493 | biostudies-literature | 2013 Sep

REPOSITORIES: biostudies-literature