| Literature DB >> 30664690 |
Hyo Won Chang1, Mi Ra Kim2, Hyang Ju Lee3, Hye Min Lee1, Gui Chul Kim1, Yoon Sun Lee1, Hae Yun Nam3, Myungjin Lee1, Hye Jin Jang1, Kyung Eun Lee4, Jong Cheol Lee5, Youngro Byun6, Seong Who Kim7, Sang Yoon Kim8,9.
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.Entities:
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Year: 2019 PMID： 30664690 DOI： 10.1038/s41388-019-0697-6
Source DB: PubMed Journal: Oncogene ISSN： 0950-9232 Impact factor: 9.867