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癌细胞代谢:重塑线粒体枢纽。

Cancer cell metabolism: Rewiring the mitochondrial hub.

机构信息

CNC-Center for Neuroscience and Cell Biology, UC-Biotech, University of Coimbra, Biocant Park, Cantanhede, Portugal.

CNC-Center for Neuroscience and Cell Biology, UC-Biotech, University of Coimbra, Biocant Park, Cantanhede, Portugal.

出版信息

Biochim Biophys Acta Mol Basis Dis. 2021 Feb 1;1867(2):166016. doi: 10.1016/j.bbadis.2020.166016. Epub 2020 Nov 25.

Abstract

To adapt to tumoral environment conditions or even to escape chemotherapy, cells rapidly reprogram their metabolism to handle adversities and survive. Given the rapid rise of studies uncovering novel insights and therapeutic opportunities based on the role of mitochondria in tumor metabolic programing and therapeutics, this review summarizes most significant developments in the field. Taking in mind the key role of mitochondria on carcinogenesis and tumor progression due to their involvement on tumor plasticity, metabolic remodeling, and signaling re-wiring, those organelles are also potential therapeutic targets. Among other topics, we address the recent data intersecting mitochondria as of prognostic value and staging in cancer, by mitochondrial DNA (mtDNA) determination, and current inhibitors developments targeting mtDNA, OXPHOS machinery and metabolic pathways. We contribute for a holistic view of the role of mitochondria metabolism and directed therapeutics to understand tumor metabolism, to circumvent therapy resistance, and to control tumor development.

摘要

为了适应肿瘤微环境条件,甚至逃避化疗,细胞会迅速重新编程其代谢以应对逆境并存活。鉴于基于线粒体在肿瘤代谢编程和治疗中的作用揭示新见解和治疗机会的研究迅速增加,本综述总结了该领域最重要的进展。考虑到线粒体在致癌作用和肿瘤进展中的关键作用,由于它们参与肿瘤可塑性、代谢重塑和信号重排,这些细胞器也是潜在的治疗靶点。在其他主题中,我们还探讨了最近的数据,这些数据将线粒体作为癌症的预后价值和分期的指标,通过线粒体 DNA(mtDNA)的测定,以及针对 mtDNA、OXPHOS 机制和代谢途径的当前抑制剂的开发。我们为线粒体代谢和靶向治疗的作用提供了一个整体的视角,以了解肿瘤代谢,规避治疗耐药性,并控制肿瘤发展。

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