Cancer Letters ( IF 9.7 ) Pub Date : 2020-03-05 , DOI: 10.1016/j.canlet.2020.03.001 Kenta Masui 1 , Mio Harachi 1 , Webster K Cavenee 2 , Paul S Mischel 2 , Noriyuki Shibata 1
Metabolic reprogramming is a central hallmark of cancer and is driven by abnormalites of oncogenes and tumor suppressors. This enables tumor cells to obtain the macromolecular precursors and energy needed for rapid tumor growth. Accelerated metabolism also translates into cancer cell aggression through epigenetic changes. The aberrant signaling cascades activated by oncogenes coordinate metabolic reprogramming with epigenetic shifts and subsequent global transcriptional changes through the dysregulation of rate-limiting metabolic enzymes as well as by facilitating the production of intermediary metabolites. As the landscape of cancer cell metabolism has been elucidated, it is now time for this knowledge to be translated into benefit for patients. Here we review the recently identified central regulatory role for mechanistic/mammalian target of rapamycin complex 2 (mTORC2), a downstream effector of many cancer-causing mutations, in reprogramming the metabolic and epigenetic landscape. This leads to tumor cell survival and cancer drug resistance.
中文翻译:
mTOR 复合物 2 是癌症代谢和表观遗传学的整合者
代谢重编程是癌症的核心标志,由癌基因和肿瘤抑制因子的异常驱动。这使肿瘤细胞能够获得快速肿瘤生长所需的大分子前体和能量。加速的新陈代谢还通过表观遗传变化转化为癌细胞的攻击性。由癌基因激活的异常信号级联通过限速代谢酶的失调以及促进中间代谢物的产生来协调代谢重编程与表观遗传变化和随后的全局转录变化。随着癌细胞代谢的前景已经被阐明,现在是时候将这些知识转化为对患者的益处了。在这里,我们回顾了最近确定的雷帕霉素复合物 2 (mTORC2) 的机械/哺乳动物靶标(许多致癌突变的下游效应子)在重新编程代谢和表观遗传景观中的中心调节作用。这导致肿瘤细胞存活和癌症耐药性。