ZDHHC14 enhances P16 stability via palmitoylation to inhibit prostate cancer progression

Jian Zhao1, Gang Ni2, Zhichao Wu1

  • 1Department of Urology, Taihe Traditional Chinese Medical Hospital Affiliated to Anhui University of Chinese Medicine, Fuyang, China.

PubMed
Abstract

Insights

This study shows ZDHHC14 enhances P16 protein stability through palmitoylation, suppressing prostate cancer cell growth and invasion. This discovery offers new therapeutic targets for prostate cancer treatment.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Prostate cancer progression involves tumor suppressor gene dysregulation.
  • P16 (CDKN2A) is a key cell cycle regulator often downregulated in cancer.
  • The role of P16 palmitoylation in prostate cancer remains largely unknown.

Purpose of the Study:

  • To investigate how palmitoylation regulates P16 stability.
  • To explore the function of ZDHHC14 in P16 palmitoylation.
  • To assess the impact of this mechanism on prostate cancer cell malignancy.

Main Methods:

  • Overexpression of CDKN2A in prostate cancer cell lines (PC-3, DU-145).
  • Assays for proliferation, migration, invasion, and protein analysis (qRT-PCR, Western blot, Transwell).
  • Analysis of P16 palmitoylation (Cys 72 site) using inhibitors, mutagenesis, ubiquitination assays, and molecular docking; ZDHHC14 interaction confirmed via siRNA and Co-IP.

Main Results:

  • P16 overexpression significantly inhibited prostate cancer cell proliferation, migration, and invasion.
  • Palmitoylation at Cys 72 stabilized P16 by reducing ubiquitination-dependent degradation.
  • ZDHHC14 was identified as the P16 palmitoyltransferase, with its expression correlating positively with patient survival.

Conclusions:

  • ZDHHC14-mediated palmitoylation of P16 at Cys 72 enhances protein stability and suppresses prostate cancer malignancy.
  • This mechanism involves inhibiting ubiquitination-dependent degradation, exerting antitumor effects.
  • The ZDHHC14/P16 axis presents a potential therapeutic target for prostate cancer.

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