Stem Cell Reviews and Reports ( IF 4.5 ) Pub Date : 2021-08-05 , DOI: 10.1007/s12015-021-10216-9 Prajna Paramita Naik 1, 2 , Swagatika Panigrahi 2 , Ratnakar Parida 2 , Prakash Priyadarshi Praharaj 1 , Chandra Sekhar Bhol 1 , Shankargouda Patil 3 , Nml Manjunath 4 , Dipanjan Ghosh 5 , Samir Kumar Patra 6 , Sujit Kumar Bhutia 1
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Cancer stem cells (CSCs) are rare populations of malignant cells with stem cell-like features of self-renewal, uninterrupted differentiation, tumorigenicity, and resistance to conventional therapeutic agents, and these cells have a decisive role in treatment failure and tumor relapse. The self-renewal potential of CSCs with atypical activation of developmental signaling pathways involves the maintenance of stemness to support cancer progression. The acquisition of stemness in CSCs has been accomplished through genetic and epigenetic rewiring following the metabolic switch. In this context, “metabostemness” denotes the metabolic parameters that essentially govern the epitranscriptional gene reprogramming mechanism to dedifferentiate tumor cells into CSCs. Several metabolites often referred to as oncometabolites can directly remodel chromatin structure and thereby influence the operation of epitranscriptional circuits. This integrated metaboloepigenetic dimension of CSCs favors the differentiated cells to move in dedifferentiated macrostates. Some metabolic events might perform as early drivers of epitranscriptional reprogramming; however, subsequent metabolic hits may govern the retention of stemness properties in the tumor mass. Interestingly, selective removal of mitochondria through autophagy can promote metabolic plasticity and alter metabolic states during differentiation and dedifferentiation. In this connection, novel metabostemness-specific drugs can be generated as potential cancer therapeutics to target the metaboloepigenetic circuitry to eliminate CSCs.
Graphical abstract
中文翻译：
癌症中的代谢：在重塑癌症干细胞中将代谢表观遗传学和线粒体自噬联系起来
癌症干细胞（CSCs）是一种罕见的恶性细胞群体，具有自我更新、不间断分化、致瘤性和对常规治疗药物耐药等干细胞样特征，这些细胞在治疗失败和肿瘤复发中起决定性作用。具有非典型发育信号通路激活的 CSC 的自我更新潜力涉及维持干性以支持癌症进展。CSC 中干性的获得是通过代谢转换后的遗传和表观遗传重新布线来完成的。在这种情况下，“代谢”表示基本上控制表观转录基因重编程机制以将肿瘤细胞去分化为 CSC 的代谢参数。几种通常被称为癌代谢物的代谢物可以直接重塑染色质结构，从而影响外转录回路的运行。CSC 的这种综合代谢表观遗传维度有利于分化细胞在去分化的宏观状态中移动。一些代谢事件可能是表观转录重编程的早期驱动因素；然而，随后的代谢命中可能会控制肿瘤块中干性特性的保留。有趣的是，通过自噬选择性去除线粒体可以促进代谢可塑性并在分化和去分化过程中改变代谢状态。在这方面，可以产生新的代谢特异性药物作为潜在的癌症治疗剂，以靶向代谢表观遗传电路以消除 CSC。
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