Infiltrating T cells promote prostate cancer metastasis via modulation of FGF11→miRNA-541→androgen receptor (AR)→MMP9 signaling
作者： Shuai Hu , Lei Li , Shuyuan Yeh , Yun Cui , Xin Li
DOI: 10.1016/J.MOLONC.2014.07.013
关键词:
摘要: Abstract Early clinical studies suggested infiltrating T cells might be associated with poor outcomes in prostate cancer (PCa) patients. The detailed mechanisms how contribute to PCa progression, however, remained unclear. Here, we found have a better capacity recruit more CD4(+) than the surrounding normal via secreting chemokines-CXCL9. consequences of recruited then lead enhance cell invasion. Mechanism dissection revealed that function through modulation FGF11→miRNA-541 signals suppress androgen receptor (AR) signals. suppressed AR alter MMP9 promote Importantly, AR-siRNA or anti-androgen Enzalutamide also enhanced recruitment and this positive feed back regulation could Targeting these newly identified FGF11-siRNA, miRNA-541 inhibitor all led partially reverse Results from in vivo mouse models confirmed in vitro lines co-culture studies. Together, results concluded metastasis FGF11→miRNA-541→AR→MMP9 signaling. may provide us new potential therapeutic approach battle metastasis.
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