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POH1 induces Smad3 deubiquitination and promotes lung cancer metastasis

Yang Yuan1, Yixiao Li1, Xiao Wu1

  • 1Department of Human Anatomy, Histology and Embryology, Program for Cancer and Cell Biology, School of Basic Medical Sciences, Peking University International Cancer Institute, and State Key Laboratory of Molecular Oncology, Peking University Health Science Center, Beijing 100191, China.

Cancer Letters
|December 7, 2023
PubMed

Insights

POH1 stabilizes Smad3, a key protein in lung cancer progression. This deubiquitinase promotes lung adenocarcinoma (LUAD) cell invasion and metastasis, indicating POH1 as a potential therapeutic target.

Area of Science:

  • Molecular Biology
  • Oncology
  • Biochemistry

Background:

  • Smad3 is crucial for TGF-β1 signaling, driving cancer cell invasion and metastasis.
  • The specific deubiquitinase that stabilizes Smad3 in lung cancer remains unidentified.

Purpose of the Study:

  • To identify the deubiquitinase responsible for Smad3 stabilization.
  • To investigate the role of this deubiquitinase in lung adenocarcinoma (LUAD) progression and metastasis.

Main Methods:

  • Investigated the interaction between POH1 and Smad3.
  • Assessed the effect of POH1 on Smad3 protein levels and half-life.
  • Evaluated POH1's impact on LUAD cell proliferation, migration, invasion, and metastasis in vitro and in vivo.

Main Results:

  • POH1 was identified as a novel deubiquitinase of Smad3.
  • POH1 directly interacts with Smad3, removing poly-ubiquitination and increasing its stability.
  • POH1 enhances LUAD cell proliferation, migration, invasion, and liver metastasis.
  • Elevated POH1 and Smad3 levels in LUAD patient tumors correlate with poor prognosis.

Conclusions:

  • POH1 acts as an oncoprotein by stabilizing Smad3 and enhancing TGF-β1/Smad3 signaling.
  • POH1 promotes LUAD metastasis, presenting a potential therapeutic target for lung cancer treatment.
Keywords:
DeubiquitinationLung cancerMetastasisPOH1Smad3

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