REV3L的缺失促进顺铂处理的肺癌细胞中p53调控的癌细胞代谢。
Absence of REV3L promotes p53-regulated cancer cell metabolism in cisplatin-treated lung carcinoma cells.
作者信息
Kong Linghao, Murata Michael M, Digman Michelle A
机构信息
Laboratory for Fluorescence Dynamics, Department of Biomedical Engineering, University of California, Irvine, CA 92697, USA; University High School, Irvine, CA 92612, USA.
Laboratory for Fluorescence Dynamics, Department of Biomedical Engineering, University of California, Irvine, CA 92697, USA.
出版信息
Biochem Biophys Res Commun. 2018 Jan 29;496(1):199-204. doi: 10.1016/j.bbrc.2018.01.026. Epub 2018 Jan 4.
Lung cancer is one of the deadliest cancers in the world because of chemo-resistance to the commonly used cisplatin-based treatments. The use of low fidelity DNA polymerases in the translesional synthesis (TLS) DNA damage response pathway that repairs lesions caused by cisplatin also presents a mutational carcinogenic burden on cells that needs to be regulated by the tumor suppressor protein p53. However, there is much debate over the roles of the reversionless 3-like (REV3L) protein responsible for TLS and p53 in regulating cancer cell metabolism. In this study, the fluorescence lifetime of the metabolic coenzyme NADH reveals that the absence of REV3L can promote the p53-mediated upregulation of oxidative phosphorylation in cisplatin-treated H1299 lung carcinoma cells and increases cancer cell sensitivity to this platinum-based chemotherapy. These results demonstrate a previously unrecognized relationship between p53 and REV3L in cancer cell metabolism and may lead to improvements in chemotherapy treatment plans that reduce cisplatin resistance in lung cancer.
由于对常用的基于顺铂的治疗产生化疗耐药性，肺癌是世界上最致命的癌症之一。在跨损伤合成（TLS）DNA损伤反应途径中使用低保真度DNA聚合酶来修复由顺铂引起的损伤，这也给细胞带来了突变致癌负担，而这种负担需要由肿瘤抑制蛋白p53来调节。然而，负责TLS的无回复3样（REV3L）蛋白和p53在调节癌细胞代谢中的作用存在很多争议。在这项研究中，代谢辅酶NADH的荧光寿命表明，缺乏REV3L可促进p53介导的顺铂处理的H1299肺癌细胞中氧化磷酸化的上调，并增加癌细胞对这种铂类化疗的敏感性。这些结果证明了p53和REV3L在癌细胞代谢中存在以前未被认识到的关系，并且可能会改进化疗治疗方案，以降低肺癌中的顺铂耐药性。
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