Institute of Biochemistry and Clinical Biochemistry, School of Medicine, Catholic University, Rome, Italy.
Adv Exp Med Biol. 2019;1158:1-16. doi: 10.1007/978-981-13-8367-0_1.
Given the role of mitochondria in modulating many cellular functions, it is not surprising that they can play a crucial role also in molecular pathophysiology of cancer. In particular, the discovery in recent decades of a link between cancer metabolic processes, alterations of mitochondrial DNA, oncogenes and tumor suppressors has led not only to a renaissance of interest in Warburg's pioneering work, but also to a reexamination of his original observations above all in relation to the current knowledge in cancer cell metabolism. It follows that, although mitochondrial contribution to the pathogenesis of cancer has historically tended to be neglected, it is now evident that reprogrammed mitochondria can contribute to a complex bioenergetic adjustment that sustains not only tumor formation but also its progression. Most importantly, cancer cell metabolism seems to have a role in diversified aspects related to cancer pathophysiology (i.e., aggressiveness, recurrence, metastatic dissemination). Hence, it is imperative to always consider cancer cell metabolism, its adaptability, its influences but, above all, its functional heterogeneity in a single tumor, for a really rational and valid approach towards molecular biology of cancer.
鉴于线粒体在调节许多细胞功能方面的作用,它们在癌症的分子病理生理学中也能发挥关键作用,这并不奇怪。特别是,近几十年来发现癌症代谢过程、线粒体 DNA 改变、癌基因和肿瘤抑制基因之间存在联系,这不仅使人们对沃伯格开创性工作的兴趣重新焕发,而且还重新审视了他的原始观察结果,尤其是与癌症细胞代谢的当前知识有关。因此,尽管线粒体对癌症发病机制的贡献在历史上一直被忽视,但现在很明显,重编程的线粒体可以有助于维持肿瘤形成及其进展的复杂生物能量调节。最重要的是,癌细胞代谢似乎在与癌症病理生理学相关的多方面都具有作用(即侵袭性、复发、转移性扩散)。因此,对于癌症的分子生物学研究,必须始终考虑癌细胞代谢及其适应性、影响,尤其是单个肿瘤中的功能异质性,这是一种真正合理和有效的方法。