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基于微管的线粒体动力学作为癌症中有价值的治疗靶点

Microtubule-Based Mitochondrial Dynamics as a Valuable Therapeutic Target in Cancer.

作者信息

Vona Rosa, Mileo Anna Maria, Matarrese Paola

机构信息

Center for Gender-Specific Medicine, Oncology Unit, Istituto Superiore di Sanità, 00161 Rome, Italy.

Tumor Immunology and Immunotherapy Unit, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS)-Regina Elena National Cancer Institute, 00144 Rome, Italy.

出版信息

Cancers (Basel). 2021 Nov 19;13(22):5812. doi: 10.3390/cancers13225812.

Abstract

Mitochondria constitute an ever-reorganizing dynamic network that plays a key role in several fundamental cellular functions, including the regulation of metabolism, energy production, calcium homeostasis, production of reactive oxygen species, and programmed cell death. Each of these activities can be found to be impaired in cancer cells. It has been reported that mitochondrial dynamics are actively involved in both tumorigenesis and metabolic plasticity, allowing cancer cells to adapt to unfavorable environmental conditions and, thus, contributing to tumor progression. The mitochondrial dynamics include fusion, fragmentation, intracellular trafficking responsible for redistributing the organelle within the cell, biogenesis, and mitophagy. Although the mitochondrial dynamics are driven by the cytoskeleton-particularly by the microtubules and the microtubule-associated motor proteins dynein and kinesin-the molecular mechanisms regulating these complex processes are not yet fully understood. More recently, an exchange of mitochondria between stromal and cancer cells has also been described. The advantage of mitochondrial transfer in tumor cells results in benefits to cell survival, proliferation, and spreading. Therefore, understanding the molecular mechanisms that regulate mitochondrial trafficking can potentially be important for identifying new molecular targets in cancer therapy to interfere specifically with tumor dissemination processes.

摘要

线粒体构成了一个不断重组的动态网络,在几个基本的细胞功能中发挥关键作用,包括代谢调节、能量产生、钙稳态、活性氧的产生以及程序性细胞死亡。在癌细胞中,这些活动中的每一项都可能受损。据报道,线粒体动态变化积极参与肿瘤发生和代谢可塑性,使癌细胞能够适应不利的环境条件,从而促进肿瘤进展。线粒体动态变化包括融合、分裂、负责在细胞内重新分布细胞器的细胞内运输、生物发生和线粒体自噬。尽管线粒体动态变化是由细胞骨架驱动的,特别是由微管以及与微管相关的运动蛋白动力蛋白和驱动蛋白驱动的,但调节这些复杂过程的分子机制尚未完全了解。最近,也有文献描述了基质细胞和癌细胞之间线粒体的交换。肿瘤细胞中线粒体转移的优势在于对细胞存活、增殖和扩散有益。因此,了解调节线粒体运输的分子机制可能对确定癌症治疗中的新分子靶点以特异性干扰肿瘤扩散过程具有重要意义。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f21d/8616325/a85b247a18f2/cancers-13-05812-g001.jpg

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