The mTOR Complexes in Cancer Cell Metabolism

Abstract

Cells metabolize nutrients to generate energy and building materials for growth and proliferation. In highly proliferating cells, such as cancer cells, there is an increased demand for nutrients with concomitant rerouting of metabolic pathways in favor of biosynthetic processes. This rewiring is accomplished by cross talk between growth signaling and metabolic pathways. At the hub of these pathways is the mechanistic or mammalian target of rapamycin (mTOR), a protein kinase that senses nutrients and growth signals. mTOR forms two protein complexes, termed mTOR complex 1 (mTORC1) and mTORC2, by partnering with distinct proteins. Several studies strongly support a central role for mTORC1 in metabolic reprogramming but there is also emerging evidence for mTORC2 involvement in this process. This review focuses on the role of both complexes in different metabolic and biosynthetic processes in which they have been linked so far, with special emphasis on the role of mTORCs in cancer metabolic reprogramming. We also discuss the clinical relevance of targeting mTOR and metabolic pathways for cancer therapy.