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AIF inhibits tumor metastasis by protecting PTEN from oxidation

Shao-Ming Shen1, Meng Guo1, Zhong Xiong1

  • 1Department of Pathophysiology, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Shanghai Jiao Tong University School of Medicine (SJTU-SM), Shanghai, China.

EMBO Reports
|September 30, 2015
PubMed

Insights

Apoptosis-inducing factor (AIF) protects the tumor suppressor PTEN from oxidation, thereby inhibiting cancer cell signaling, epithelial-mesenchymal transition, and metastasis. AIF’s role in controlling tumor spread is linked to patient survival.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Cell Biology

Background:

  • Apoptosis-inducing factor (AIF) has dual roles in cell death and survival, with its substrates and role in tumorigenesis unclear.
  • PTEN, a tumor suppressor, is prone to inactivation via oxidation.

Purpose of the Study:

  • To identify AIF substrates and elucidate its role in cancer.
  • To investigate the interaction between AIF and PTEN and its impact on cancer progression.

Main Methods:

  • Co-immunoprecipitation to assess AIF-PTEN interaction.
  • Assessment of PTEN lipid phosphatase activity and Akt phosphorylation.
  • Analysis of β-catenin signaling, EMT, and metastasis in vitro and in vivo.
  • Correlation of AIF expression with patient survival data.

Main Results:

  • AIF directly interacts with and inhibits the oxidation and inactivation of PTEN.
  • AIF knockdown leads to PTEN inactivation, Akt activation, and subsequent β-catenin signaling activation.
  • AIF inhibits EMT and metastasis by modulating β-catenin signaling.
  • AIF expression correlates with improved survival in multiple cancer types.

Conclusions:

  • PTEN is identified as a substrate of AIF oxidoreductase.
  • AIF plays a crucial role in suppressing tumor metastasis through PTEN regulation.
  • AIF expression is a potential prognostic biomarker for cancer patients.
Keywords:
AIFPTENcancer metastasisoxidationβ‐catenin signaling

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