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CTEN Is a Novel ΔNp63α Target for the Regulation of Prostate Cell Adhesion and Is Associated with Prostate Cancer Progression
Author(s) -
Liao YiChun,
Wu WeiMing,
Yang Kuan,
Chen YaChi,
Lo Su Hao
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.1055.5
Subject(s) - gene silencing , transcription factor , cell adhesion , chromatin immunoprecipitation , prostate cancer , cancer research , biology , focal adhesion , microbiology and biotechnology , promoter , signal transduction , cancer , cell , gene expression , gene , genetics
p63 is a member of the p53 transcription factor family and a linchpin of epithelial development and homeostasis. p63 drives the expression of many target genes involved in cell survival, adhesion, migration and cancer. In this study, we identify CTEN as a downstream target of ΔNp63α, the predominant p63 isoform expressed in epithelium. ΔNp63 and CTEN are both highly expressed in normal prostate epithelial cells and are down‐regulated in prostate cancer. In addition, reduced expression of CTEN and ΔNp63 is correlated with prostate cancer progression from primary tumors to metastatic lesions. Silencing of ΔNp63 leads to decreased mRNA and protein levels of CTEN. ΔNp63α induces transcriptional activity of the CTEN promoter and a 140‐bp fragment upstream of the transcription initiation site is the minimal promoter region required for activation. A putative binding site for p63 is located between −61 and −36 within the CTEN promoter and mutations of the critical nucleotides in this region abolish ΔNp63α‐induced promoter activity. The direct interaction of ΔNp63α with the CTEN promoter was demonstrated using a chromatin immunoprecipitation (ChIP) assay. Moreover, impaired cell adhesion caused by ΔNp63α depletion is rescued by over‐expression of CTEN, suggesting that CTEN is a downstream effector of ΔNp63α‐mediated cell adhesion. In summary, our findings demonstrate that ΔNp63α functions as a trans‐activation factor of CTEN promoter and regulates cell adhesion through modulating CTEN. Our study further contributes to the potential regulatory mechanisms of CTEN in prostate cancer progression. Support or Funding Information This study was supported by grants from the Ministry of Science and Technology, Taiwan (NSC‐102‐2628‐B‐002‐028‐MY3) and National Taiwan University (NTU‐CESRP‐104R76262).