p53/BNIP3-dependent mitophagy limits glycolytic shift in radioresistant cancer

Hyo Won Chang1, Mi Ra Kim2, Hyang Ju Lee3

  • 1Department of Otolaryngology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.

Oncogene
|January 22, 2019
PubMed

Insights

This study reveals that p53 protein prevents cancer cells from shifting to glycolysis after radiation. Targeting glycolysis may overcome radioresistant cancers, with p53 status guiding patient selection.

Area of Science:

  • Oncology
  • Cancer Metabolism
  • Molecular Biology

Background:

  • The role of p53 in metabolic shifts induced by genotoxic cancer therapies remains unclear.
  • Understanding these shifts is crucial for developing effective cancer treatments.

Purpose of the Study:

  • To investigate the function of p53 in the metabolic reprogramming of head and neck squamous cell carcinoma cells post-irradiation.
  • To explore the link between p53, mitophagy, and metabolic adaptation in radioresistant cancer cells.

Main Methods:

  • Established isogenic p53-null and wild-type radioresistant head and neck squamous cell carcinoma cell lines.
  • Assessed cellular respiration, glycolysis, mitochondrial integrity, and mitophagy.
  • Investigated the role of BNIP3 in p53-mediated mitophagy.

Main Results:

  • p53-null cells exhibited decreased oxygen consumption, increased glycolysis, and mitochondrial dysfunction, enhancing sensitivity to glycolysis inhibitors.
  • Wild-type p53 cells maintained metabolic profiles and mitochondrial integrity via mitophagy.
  • A novel p53-mitophagy pathway (BNIP3-dependent) was identified, limiting the glycolytic shift by clearing damaged mitochondria.

Conclusions:

  • p53 plays a critical role in preventing radioresistant cancer cells from adopting a glycolytic phenotype.
  • Targeting glycolysis presents a potential strategy to treat radioresistant cancers.
  • p53 status can serve as a biomarker for patient stratification in clinical trials for glycolysis-targeting drugs.

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