MTOR complex 2 is an integrator of cancer metabolism and epigenetics. (28th May 2020)

• Record Type: Journal Article
• Authors: Masui, Kenta; Harachi, Mio; Cavenee, Webster K.; Mischel, Paul S.; Shibata, Noriyuki
• Is Part Of: Cancer letters. Volume 478(2020)
• Page Start: 1
• Page End: 7
• Publication Date: 2020-05-28
• Subjects: mTOR complex -- Metabolic reprogramming -- Microenvironment -- Histone acetylation -- Iron metabolism; Cancer -- Periodicals; Neoplasms -- Periodicals; Cancer -- Périodiques; Electronic journals; 616.994
• DOI: 10.1016/j.canlet.2020.03.001
• Languages: English
• ISSNs: 0304-3835

Abstract

Abstract: 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. Highlights: MTORC2 works as a nutrient sensor as well as metabolic driver in cancer cells. MTORC2 reprograms metabolic and epigenetic landscape in cancer. Glucose-driven epigenetic reprogramming is linked to iron metabolism.