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Yeast As a Chassis for Developing Functional Assays to Study Human P53
14:57

Yeast As a Chassis for Developing Functional Assays to Study Human P53

Published on: August 4, 2019

Mitophagy Controls the Activities of Tumor Suppressor p53 to Regulate Hepatic Cancer Stem Cells

Kai Liu1, Jiyoung Lee2, Ja Yeon Kim2

  • 1Department of Molecular Microbiology and Immunology, University of Southern California Keck School of Medicine, Los Angeles, CA 90033, USA; Beijing You'an Hospital, Capital Medical University, Beijing 100069, China; Beijing Institute of Hepatology, Beijing 100069, China.

Molecular Cell
|October 17, 2017
PubMed

Insights

Mitophagy, a process removing damaged mitochondria, promotes liver cancer by suppressing the tumor suppressor p53. Inhibiting mitophagy boosts p53, reducing cancer stem cells and liver tumor growth.

Area of Science:

  • Cell Biology
  • Cancer Research
  • Hepatology

Background:

  • Autophagy, a cellular degradation process, is implicated in the progression of benign liver tumors to malignant hepatocellular carcinoma.
  • The precise mechanisms by which autophagy influences hepatocarcinogenesis, particularly involving cancer stem cells, remain incompletely understood.

Purpose of the Study:

  • To elucidate the role of mitophagy, a specific type of autophagy, in regulating hepatic cancer stem cells (CSCs) and their associated molecular pathways.
  • To investigate the interaction between mitophagy, the tumor suppressor p53, and key stemness factors in hepatocellular carcinoma.

Main Methods:

  • Investigated the effect of enhanced and inhibited mitophagy on p53 localization and activity in hepatic cells.
  • Utilized western blotting and immunofluorescence to assess p53 phosphorylation, mitochondrial co-localization, and nuclear translocation.
  • Analyzed the impact of mitophagy modulation on the expression of NANOG, OCT4, and SOX2 in hepatic CSCs.

Main Results:

  • Enhanced mitophagy leads to the degradation of p53 in a mitophagy-dependent manner, thereby promoting CSCs.
  • Inhibition of mitophagy results in PINK1-mediated phosphorylation of p53 on mitochondria.
  • Phosphorylated p53 translocates to the nucleus, binds the NANOG promoter, and suppresses OCT4/SOX2, reducing hepatic CSC populations.

Conclusions:

  • Mitophagy positively regulates hepatic CSCs by controlling p53 activity and stability.
  • The study reveals a novel mechanism linking mitophagy to p53 regulation, explaining autophagy's role in promoting hepatocarcinogenesis.
  • Targeting mitophagy could represent a therapeutic strategy for reducing hepatic CSCs in liver cancer.
Keywords:
NANOGPINK1autophagyhepatic cancer stem cellsmitophagyp53

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