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

Title
p53/BNIP3-dependent mitophagy limits glycolytic shift in radioresistant cancer
Authors
이경은장효원김미라이혜민Gui Chul KimHae Yun NamMyungjin LeeYoon Sun LeeHye Jin JangJong Cheol LeeYoungro ByunSeong Who KimSang Yoon Kim
Issue Date
2019-01
Publisher
Oncogene
Citation
VOL 38, NO 9-3742
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.
URI
http://pubs.kist.re.kr/handle/201004/69017
ISSN
0950-9232
Appears in Collections:
KIST Publication > Article
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