The PI3K, Metabolic, and Autophagy Networks: Interactive Partners in Cellular Health and Disease

Annual Review of Pharmacology and Toxicology - Tập 53 Số 1 - Trang 89-106 - 2013
Naval P. Shanware1, Kevin Bray2, Robert T. Abraham3
1Oncology Research Unit, Pfizer Worldwide Research and Development, Pearl River, New York 10965, USA.
2Oncology Research Unit, Pfizer Worldwide Research and Development, Pearl River, New York 10965
3Oncology Research Unit, Pfizer Worldwide Research and Development, San Diego, California 92121;

Tóm tắt

A fundamental imperative for mammalian cells is to coordinate cell metabolism and growth with environmentally induced stress. This review focuses on three highly integrated networks—the phosphoinositide 3-kinase (PI3K) signaling cascade, intermediate metabolism, and autophagy—that work together to maintain cellular homeostasis under basal conditions and to drive cell-mass accumulation and cell cycle progression in the presence of appropriate mitogenic stimuli. Dysfunction within any one of these networks results in compensatory responses from the other networks. These responses underpin several pathologies associated with major human diseases such as cancer. We discuss the PI3K, metabolism, and autophagy networks and provide selected insights into internetwork cross-talk mechanisms. In recognition of the extensive interactions observed in both healthy and diseased cells, we propose that the three networks be merged into a “metabolism-signaling supernetwork.” A detailed understanding of this supernetwork will facilitate the development of novel therapies for cancer and other complex diseases.

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Annual Review of Pharmacology and Toxicology

Tập 53 Số 1

89-106

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