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The Expanding Role of the mammalian Target of Rapamycin Complex 2 (mTORC2) in Cellular Metabolism

Ghada A. Soliman

The mammalian Target of Rapamycin (mTOR) nutrient-sensing pathway plays a fundamental role in cell growth, and proliferation, as well as in tumor metabolism. mTOR is the catalytic subunit that nucleates two functionally and structurally distinct complexes namely; mTORC1 (mammalian Target of Rapamycin Complex 1) and mTORC2 (mammalian Target of Rapamycin Complex 2). mTORC1 integrates inputs from nutrients, growth factors, and environmental cues; and transduces signals to downstream targets to promote anabolism and decrease catabolism. As such, mTORC1 is considered a master regulator of metabolism, cell growth, and proliferation. mTORC1 is activated by PI3K (phosphoinositide 3-kinases)-Akt/PKB (protein kinase B) and Ras- ERK ( extracellular signal-regulated kinase) pathways, both of which are the most common oncogenic signaling pathways activated in cancer. Recently, mTORC2 emerged as an important contributor to cellular and tumormetabolism. mTORC2 receives inputs mainly from growth factors and regulates the organization of actin cytoskeleton, cell survival, and cellular metabolism. This review focuses on the role of mTORC2 in cellular metabolism and cancer metabolism. Understanding the underpinning of mTORC2 signaling and targeting both mTORC1 and mTORC2 complexes, holds promise for regimens in cancer early detection, monitoring, and treatment.