Departamento de Biología Molecular, Centro de Biología Molecular Severo Ochoa, Centro de Investigación Biomédica en Red de Enfermedades Raras, Centro de Investigación Hospital 12 de Octubre, Madrid, Spain.
Antioxid Redox Signal. 2013 Jul 20;19(3):285-98. doi: 10.1089/ars.2012.4883. Epub 2012 Sep 24.
Since the signing of the National Cancer Act in 1971, cancer still remains a major cause of death despite significant progresses made in understanding the biology and treatment of the disease. After many years of ostracism, the peculiar energy metabolism of tumors has been recognized as an additional phenotypic trait of the cancer cell.
While the enhanced aerobic glycolysis of carcinomas has already been translated to bedside for precise tumor imaging and staging of cancer patients, accepting that an impaired bioenergetic function of mitochondria is pivotal to understand energy metabolism of tumors and in its progression is debated. However, mitochondrial bioenergetics and cell death are tightly connected.
Recent clinical findings indicate that H(+)-ATP synthase, a core component of mitochondrial oxidative phosphorylation, is repressed at both the protein and activity levels in human carcinomas. This review summarizes the relevance that mitochondrial function has to understand energy metabolism of tumors and explores the connection between the bioenergetic function of the organelle and the activity of mitochondria as tumor suppressors.
The reversible nature of energy metabolism in tumors highlights the relevance that the microenvironment has for tumor progression. Moreover, the stimulation of mitochondrial activity or the inhibition of glycolysis suppresses tumor growth. Future research should elucidate the mechanisms promoting the silencing of oxidative phosphorylation in carcinomas. The aim is the development of new therapeutic strategies tackling energy metabolism to eradicate tumors or at least, to maintain tumor dormancy and transform cancer into a chronic disease.
自 1971 年《国家癌症法案》签署以来，尽管在理解疾病的生物学和治疗方面取得了重大进展，但癌症仍然是主要的死亡原因。经过多年的排斥，肿瘤独特的能量代谢已被认为是癌细胞的另一个表型特征。
虽然癌细胞的有氧糖酵解已经被转化为床边技术，用于精确的肿瘤成像和癌症患者的分期，但接受线粒体生物能功能受损是理解肿瘤能量代谢及其进展的关键因素仍存在争议。然而，线粒体生物能和细胞死亡是紧密相连的。
最近的临床发现表明，人类癌组织中，线粒体氧化磷酸化的核心组成部分 H(+)-ATP 合酶在蛋白质和活性水平上均受到抑制。这篇综述总结了线粒体功能对理解肿瘤能量代谢的相关性，并探讨了细胞器的生物能功能与作为肿瘤抑制因子的线粒体活性之间的联系。
肿瘤能量代谢的可逆性强调了微环境对肿瘤进展的重要性。此外，刺激线粒体活性或抑制糖酵解会抑制肿瘤生长。未来的研究应该阐明促进癌组织中氧化磷酸化沉默的机制。目的是开发新的治疗策略来解决能量代谢问题，以根除肿瘤，或至少维持肿瘤休眠状态，将癌症转变为慢性病。
