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[癌症中的琥珀酸脱氢酶]

[Succinate dehydrogenase in cancer].

作者信息

Moog Sophie, Favier Judith

机构信息

Université de Paris, PARCC, Inserm UMR970, Équipe labellisée par la Ligue contre le cancer, Paris, France.

出版信息

Med Sci (Paris). 2022 Mar;38(3):255-262. doi: 10.1051/medsci/2022024. Epub 2022 Mar 25.

Abstract

Succinate dehydrogenase (SDH) is a mitochondrial enzyme that participates in both the tricarboxylic acid cycle and the electron transport chain. Mutations in genes encoding SDH are responsible for a predisposition to pheochromocytomas and paragangliomas, and more rarely, to gastrointestinal stromal tumors or renal cell carcinomas. A decrease in SDH activity, not explained by genetics, has also been observed in more common cancers. One of the consequences of the inactivation of SDH is the excessive production of its substrate, succinate, which acts as an oncometabolite by promoting a pseudohypoxic status and an extensive epigenetic rearrangement. Understanding SDH-related oncogenesis now makes it possible to develop innovative diagnostic methods and to consider targeted therapies for the management of affected patients.

摘要

琥珀酸脱氢酶(SDH)是一种参与三羧酸循环和电子传递链的线粒体酶。编码SDH的基因突变是嗜铬细胞瘤和副神经节瘤易感性的原因,更罕见的是,也与胃肠道间质瘤或肾细胞癌有关。在更常见的癌症中也观察到SDH活性降低,而这种降低并非由遗传因素引起。SDH失活的后果之一是其底物琥珀酸的过度产生,琥珀酸通过促进假低氧状态和广泛的表观遗传重排而作为一种致癌代谢物发挥作用。了解与SDH相关的肿瘤发生机制现在使得开发创新的诊断方法以及考虑针对受影响患者的靶向治疗成为可能。

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