Cancer and Cell Death Laboratory, Department of Life Science, National Institute of Technology Rourkela, Rourkela, Odisha, 769008, India.
P.G. Department Zoology, Vikram Deb Autonomous College, Jeypore, Koraput, Odisha, India.
Stem Cell Rev Rep. 2022 Jan;18(1):198-213. doi: 10.1007/s12015-021-10216-9. Epub 2021 Aug 5.
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.
癌症干细胞（CSC）是一种具有干细胞特征的恶性细胞群体，具有自我更新、不间断分化、致瘤性和对传统治疗药物的耐药性等特征，这些细胞在治疗失败和肿瘤复发中起着决定性的作用。CSC 的自我更新潜能与发育信号通路的非典型激活有关，涉及维持干性以支持癌症进展。CSC 中的干性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，“代谢干性”表示控制转录后基因重编程机制的代谢参数，将肿瘤细胞分化为 CSC。几种通常被称为致癌代谢物的代谢物可以直接重塑染色质结构，从而影响转录后电路的运作。CSC 的这种综合代谢表观遗传维度有利于分化细胞向去分化的宏观状态移动。一些代谢事件可能作为转录后重编程的早期驱动因素；然而，随后的代谢打击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，可以生成新型的代谢干性特异性药物作为潜在的癌症治疗药物，以针对代谢表观遗传电路来消除 CSC。
