Institute of Pharmacology, National Yang-Ming University, Taipei, 112, Taiwan.
Department of Biochemistry and Molecular Biology, National Yang-Ming University, Taipei, 112, Taiwan.
Int J Mol Sci. 2009 Feb;10(2):674-701. doi: 10.3390/ijms10020674. Epub 2009 Feb 23.
A shift in glucose metabolism from oxidative phosphorylation to glycolysis is one of the biochemical hallmarks of tumor cells. Mitochondrial defects have been proposed to play an important role in the initiation and/or progression of various types of cancer. In the past decade, a wide spectrum of mutations and depletion of mtDNA have been identified in human cancers. Moreover, it has been demonstrated that activation of oncogenes or mutation of tumor suppressor genes, such as p53, can lead to the upregulation of glycolytic enzymes or inhibition of the biogenesis or assembly of respiratory enzyme complexes such as cytochrome c oxidase. These findings may explain, at least in part, the well documented phenomena of elevated glucose uptake and mitochondrial defects in cancers. In this article, we review the somatic mtDNA alterations with clinicopathological correlations in human cancers, and their potential roles in tumorigenesis, cancer progression, and metastasis. The signaling pathways involved in the shift from aerobic metabolism to glycolysis in human cancers are also discussed.
葡萄糖代谢从氧化磷酸化向糖酵解的转变是肿瘤细胞的生化标志之一。线粒体缺陷被认为在各种类型癌症的发生和/或发展中起着重要作用。在过去的十年中，已经在人类癌症中鉴定出广泛的 mtDNA 突变和耗竭。此外，已经证明癌基因的激活或肿瘤抑制基因（如 p53）的突变可导致糖酵解酶的上调或呼吸酶复合物（如细胞色素 c 氧化酶）的生物发生或组装的抑制。这些发现至少可以部分解释在癌症中葡萄糖摄取和线粒体缺陷的现象。在本文中，我们综述了人类癌症中与临床病理相关的体细胞 mtDNA 改变及其在肿瘤发生、癌症进展和转移中的潜在作用。还讨论了人类癌症中从有氧代谢向糖酵解转变所涉及的信号通路。
