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Published on: October 30, 2013
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.
Abstract:
UNC5B is a known tumor suppressor gene in a variety of cancers. As a transmembrane protein, UNC5B also induces apoptosis in a P53-dependent manner. In this study, we demonstrate that UNC5B inhibits proliferation through G2/M phase arrest by mass spectrometry and bioinformatics analysis in bladder cancer cells. By combing with CDC14A and P53, UNC5B dephosphorylated P53 at Ser-315 site. This dephosphorylation facilitated G2/M phase arrest by reducing the expression of cyclin B1 and increasing the expression of p-CDK1, thus inhibiting tumor proliferation. Knockdown of CDC14A suppressed the G2/M phase arrest induced by UNC5B in vitro, and eliminated the inhibitory effect of UNC5B on tumor proliferation in vivo. Our results show that UNC5B-mediated cell cycle arrest may act as a potential treatment for bladder cancer.
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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