Masgras Ionica, Sanchez-Martin Carlos, Colombo Giorgio, Rasola Andrea
Dipartimento di Scienze Biomediche, Istituto di Neuroscienze, Consiglio Nazionale delle Ricerche (CNR), Università di Padova , Padova , Italy.
Istituto di Chimica del Riconoscimento Molecolare, Consiglio Nazionale delle Ricerche (CNR) , Milano , Italy.
Front Oncol. 2017 Mar 29;7:58. doi: 10.3389/fonc.2017.00058. eCollection 2017.
Mitochondria can receive, integrate, and transmit a variety of signals to shape many biochemical activities of the cell. In the process of tumor onset and growth, mitochondria contribute to the capability of cells of escaping death insults, handling changes in ROS levels, rewiring metabolism, and reprograming gene expression. Therefore, mitochondria can tune the bioenergetic and anabolic needs of neoplastic cells in a rapid and flexible way, and these adaptations are required for cell survival and proliferation in the fluctuating environment of a rapidly growing tumor mass. The molecular bases of pro-neoplastic mitochondrial adaptations are complex and only partially understood. Recently, the mitochondrial molecular chaperone TRAP1 (tumor necrosis factor receptor associated protein 1) was identified as a key regulator of mitochondrial bioenergetics in tumor cells, with a profound impact on neoplastic growth. In this review, we analyze these findings and discuss the possibility that targeting TRAP1 constitutes a new antitumor approach.
线粒体能够接收、整合并传递多种信号，从而塑造细胞的许多生化活动。在肿瘤发生和生长过程中，线粒体有助于细胞逃避死亡刺激、应对活性氧水平变化、重塑代谢以及重新编程基因表达。因此，线粒体能够以快速且灵活的方式调节肿瘤细胞的生物能量和合成代谢需求，而这些适应性变化是肿瘤快速生长、环境波动时细胞存活和增殖所必需的。肿瘤相关线粒体适应性变化的分子基础十分复杂，目前仅得到部分理解。最近，线粒体分子伴侣TRAP1（肿瘤坏死因子受体相关蛋白1）被确定为肿瘤细胞线粒体生物能量学的关键调节因子，对肿瘤生长具有深远影响。在本综述中，我们分析了这些发现，并探讨了靶向TRAP1作为一种新的抗肿瘤方法的可能性。
