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Nuclear receptor HNF4α performs a tumor suppressor function in prostate cancer via its induction of p21-driven

Zhu Wang1,2, Youjia Li2, Dinglan Wu2

  • 1Department of Urology, People's Hospital of Longhua, Southern Medical University, Shenzhen, Guangdong, 518109, China.

Oncogene
|November 8, 2019
PubMed

Insights

Hepatocyte nuclear factor 4α (HNF4α) acts as a tumor suppressor in prostate cancer. Reduced HNF4α promotes cancer cell proliferation and resistance to chemotherapy, while its overexpression induces senescence.

Area of Science:

  • Molecular Biology
  • Oncology
  • Genetics

Background:

  • Hepatocyte nuclear factor 4α (HNF4α) is a nuclear receptor involved in xenobiotic metabolism and gastrointestinal cancers.
  • Its role in prostate cancer progression remains unclear.

Purpose of the Study:

  • To investigate the functional significance of HNF4α in prostate cancer.

Main Methods:

  • Assessed HNF4α expression in prostate cancer tissues and cell lines.
  • Utilized stable HNF4α knockdown and overexpression models.
  • Evaluated effects on cell proliferation, senescence, drug resistance, and tumorigenicity.
  • Investigated the p21 signaling pathway and CDKN1A transactivation.

Main Results:

  • HNF4α expression was reduced in prostate cancer.
  • HNF4α knockdown enhanced proliferation, suppressed doxorubicin-induced senescence, and increased resistance to paclitaxel.
  • HNF4α overexpression inhibited proliferation, induced G2/M cell-cycle arrest, and triggered p53-independent senescence via p21 activation.

Conclusions:

  • HNF4α functions as a tumor suppressor in prostate cancer.
  • Its mechanism involves promoting p21-driven cellular senescence.

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