mTOR complex 2 is an integrator of cancer metabolism and epigenetics

Cancer Lett. 2020 May 28:478:1-7. doi: 10.1016/j.canlet.2020.03.001. Epub 2020 Mar 5.

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.

Keywords: Histone acetylation; Iron metabolism; Metabolic reprogramming; Microenvironment; mTOR complex.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Epigenesis, Genetic
  • Gene Expression Regulation, Neoplastic
  • Gene Regulatory Networks*
  • Glycolysis
  • Humans
  • Mechanistic Target of Rapamycin Complex 2 / metabolism*
  • Mutation
  • Neoplasms / genetics
  • Neoplasms / metabolism*

Substances

  • Mechanistic Target of Rapamycin Complex 2