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

Abstract:

:The role of p53 in genotoxic therapy-induced metabolic shift in cancers is not yet known. In this study, we investigated the role of p53 in the glycolytic shift in head and neck squamous cell carcinoma cell lines following irradiation. Isogenic p53-null radioresistant cancer cells established through cumulative irradiation showed decreased oxygen consumption and increased glycolysis with compromised mitochondria, corresponding with their enhanced sensitivity to drugs that target glycolysis. In contrast, radioresistant cancer cells with wild-type p53 preserved their primary metabolic profile with intact mitophagic processes and maintained their mitochondrial integrity. Moreover, we identified a previously unappreciated link between p53 and mitophagy, which limited the glycolytic shift through the BNIP3-dependent clearance of abnormal mitochondria. Thus, drugs targeting glycolysis could be used as an alternative strategy for overcoming radioresistant cancers, and the p53 status could be used as a biomarker for selecting participants for clinical trials.

journal_name

Oncogene

journal_title

Oncogene

authors

Chang HW,Kim MR,Lee HJ,Lee HM,Kim GC,Lee YS,Nam HY,Lee M,Jang HJ,Lee KE,Lee JC,Byun Y,Kim SW,Kim SY

doi

10.1038/s41388-019-0697-6

subject

Has Abstract

pub_date

2019-05-01 00:00:00

pages

3729-3742

issue

19

eissn

0950-9232

issn

1476-5594

pii

10.1038/s41388-019-0697-6

journal_volume

38

pub_type

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