KLF4 functions as an activator of the androgen receptor through reciprocal feedback

M-K Siu, F Suau, W-Y Chen, Y-C Tsai, H-Y Tsai, H-L Yeh, Y-N Liu

Research output: Contribution to journalArticlepeer-review

17 Citations (Scopus)


In prostate cancer, Krüppel-like factor 4 (KLF4) depletion occurs frequently, suggesting a role as suppressor tumor. KLF4 is a transcription factor associated with androgen receptor (AR) expression; however, its cellular functions and signaling regulation mechanism remain largely unknown. In this study, we demonstrated that activated AR binds to the KLF4 promoter and enhances KLF4 expression, which reciprocally targets the AR promoter, thus sustaining KLF4 activity. Ectopic KLF4 expression in androgen-independent prostate cancer cells induced AR expression and decreased cell proliferation, invasion and bone metastasis. We previously showed that increased microRNA (miR)-1 expression is associated with reduced bone metastasis of prostate cancer cells. Here we observed that KLF4 targets the primary miR-1-2 stem-loop promoter and stimulates miR-1 expression. In clinical prostate cancer specimens, KLF4 levels were positively correlated with miR-1 and AR levels. These data suggest that the loss of KLF4 expression is one mechanistic link between aggressive prostate cancer progression and low canonical AR output through miR-1 inactivation.
Original languageEnglish
Pages (from-to)e282
Issue number12
Publication statusPublished - Dec 2016


Dive into the research topics of 'KLF4 functions as an activator of the androgen receptor through reciprocal feedback'. Together they form a unique fingerprint.

Cite this