1. Academic Validation
  2. KLF5 Is Crucial for Androgen-AR Signaling to Transactivate Genes and Promote Cell Proliferation in Prostate Cancer Cells

KLF5 Is Crucial for Androgen-AR Signaling to Transactivate Genes and Promote Cell Proliferation in Prostate Cancer Cells

  • Cancers (Basel). 2020 Mar 21;12(3):748. doi: 10.3390/cancers12030748.
Juan Li 1 2 Baotong Zhang 3 Mingcheng Liu 1 2 Xing Fu 1 2 Xinpei Ci 4 Jun A 1 2 Changying Fu 1 2 Ge Dong 1 Rui Wu 1 2 Zhiqian Zhang 2 Liya Fu 1 Jin-Tang Dong 2 3
Affiliations

Affiliations

  • 1 Department of Genetics and Cell Biology, College of Life Sciences, Nankai University, 94 Weijin Road, Tianjin 300071, China.
  • 2 School of Medicine, Southern University of Science and Technology, 1088 Xueyuan Road, Shenzhen, Guangdong 518055, China.
  • 3 Emory Winship Cancer Institute, Department of Hematology and Medical Oncology, Emory University School of Medicine, 1365-C Clifton Road, Atlanta, GA 30322, USA.
  • 4 Vancouver Prostate Centre, Department of Urologic Sciences, University of British Columbia, Vancouver, BC V6H 3Z6, Canada.
Abstract

Androgen/Androgen Receptor (AR) signaling drives both the normal prostate development and prostatic carcinogenesis, and patients with advanced prostate Cancer often develop resistance to androgen deprivation therapy. The transcription factor Krüppel-like factor 5 (KLF5) also regulates both normal and cancerous development of the prostate. In this study, we tested whether and how KLF5 plays a role in the function of AR signaling in prostate Cancer cells. We found that KLF5 is upregulated by androgen depending on AR in LNCaP and C4-2B cells. Silencing KLF5, in turn, reduced AR transcriptional activity and inhibited androgen-induced cell proliferation and tumor growth in vitro and in vivo. Mechanistically, KLF5 occupied the promoter of AR, and silencing KLF5 repressed AR transcription. In addition, KLF5 and AR physically interacted with each other to regulate the expression of multiple genes (e.g., MYC, CCND1 and PSA) to promote cell proliferation. These findings indicate that, while transcriptionally upregulated by AR signaling, KLF5 also regulates the expression and transcriptional activity of AR in androgen-sensitive prostate Cancer cells. The KLF5-AR interaction could provide a therapeutic opportunity for the treatment of prostate Cancer.

Keywords

KLF5; androgen receptor; cell proliferation; prostate cancer; tumorigenesis.

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