Transcriptional Control of Cellular Metabolism by mTOR Signaling

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Abstract
Tumor cells are characterized by adaptations in cellular metabolism that afford growth and proliferative advantages over normal cells and, thus, contribute to cancer pathophysiology. There is an increasing appreciation of the fact that oncogenic signaling controls the metabolic reprogramming of cancer cells; however, the mechanisms and critical players are only beginning to be elucidated. Recent studies have revealed that mTOR complex 1 (mTORC1), a master regulator of cell growth and proliferation downstream of oncogenic signaling pathways, controls specific aspects of cellular metabolism through the induction of metabolic gene expression. mTORC1 activation is sufficient to promote flux through glycolysis and the oxidative branch of the pentose phosphate pathway, as well as to stimulate de novo lipogenesis, all processes that are important in tumor biology. As mTORC1 signaling is aberrantly elevated in the majority of genetic tumor syndromes and sporadic cancers, this pathway is poised to be a major driver of the metabolic conversion of tumor cells. Cancer Res; 71(8); 2815–20. ©2011 AACR.