UNC5B mediates G2/M phase arrest of bladder cancer cells by binding to CDC14A and P53

Yexiang Huang1, Yuyan Zhu1, Zhe Zhang1

  • 1Department of Urology, The First Hospital of China Medical University, Shenyang, 110001, China.

Insights

UNC5B, a tumor suppressor, inhibits bladder cancer cell proliferation by inducing cell cycle arrest. This occurs through dephosphorylation of P53, offering a potential new treatment strategy.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Cycle Regulation

Background:

  • UNC5B functions as a tumor suppressor gene across various cancers.
  • UNC5B, a transmembrane protein, can induce apoptosis in a P53-dependent manner.

Purpose of the Study:

  • To investigate the mechanism by which UNC5B inhibits proliferation in bladder cancer cells.
  • To explore the role of UNC5B in cell cycle regulation and its interaction with P53 and CDC14A.

Main Methods:

  • Mass spectrometry and bioinformatics analysis were employed to study UNC5B in bladder cancer cells.
  • Investigated the interaction of UNC5B with CDC14A and P53, focusing on P53 dephosphorylation at Ser-315.
  • Assessed the impact of UNC5B and CDC14A on cell cycle progression and tumor proliferation in vitro and in vivo.

Main Results:

  • UNC5B inhibits bladder cancer cell proliferation by inducing G2/M phase arrest.
  • UNC5B, in complex with CDC14A and P53, dephosphorylates P53 at Ser-315, leading to cell cycle arrest.
  • Reduced cyclin B1 expression and increased p-CDK1 expression were observed, contributing to proliferation inhibition.
  • Knockdown of CDC14A abrogated UNC5B-induced G2/M arrest and tumor growth inhibition.

Conclusions:

  • UNC5B-mediated G2/M phase arrest, through P53 dephosphorylation, is a key mechanism inhibiting bladder cancer proliferation.
  • The UNC5B-CDC14A-P53 pathway presents a potential therapeutic target for bladder cancer treatment.

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