Cytosolic FoxO1 is essential for the induction of autophagy and tumour suppressor activity

Ying Zhao1, Jing Yang, Wenjuan Liao

  • 1Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Biochemistry and Molecular Biology, Peking University Health Science Center, Beijing 100191, China.

Nature Cell Biology
|June 15, 2010
PubMed

Insights

Cytosolic Forkhead O1 (FoxO1) protein mediates autophagy, a cellular process crucial for tumor suppression. This mechanism involves FoxO1 acetylation and interaction with Atg7, leading to cancer cell death and demonstrating FoxO1

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Oncology

Background:

  • Autophagy degrades cellular components but its role in tumor suppression is unclear.
  • Forkhead O (FoxO) proteins are implicated in various cellular processes, including stress response and cancer.

Purpose of the Study:

  • To investigate the role of cytosolic Forkhead O1 (FoxO1) in mediating autophagy.
  • To elucidate the mechanism by which FoxO1 influences autophagy and its connection to tumor suppression.

Main Methods:

  • Utilized human cancer cell lines and a xenograft mouse model.
  • Investigated endogenous FoxO1 requirement for autophagy under oxidative stress and serum starvation.
  • Analyzed FoxO1 acetylation, its dissociation from sirtuin-2 (SIRT2), and its binding to Atg7.

Main Results:

  • Endogenous FoxO1 is essential for autophagy induction in cancer cells.
  • FoxO1's role in autophagy is independent of its transcriptional activity.
  • Stress-induced FoxO1 acetylation and subsequent binding to Atg7 modulate autophagy, promoting cell death.
  • FoxO1-mediated cell death exhibits tumor suppressor activity in preclinical models.

Conclusions:

  • Cytosolic FoxO1 acts as a key mediator of autophagy.
  • FoxO1's interaction with SIRT2 and Atg7 links autophagy to cancer cell death.
  • This pathway highlights the anti-neoplastic activity of FoxO1 and its connection to autophagy, offering potential therapeutic insights.

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