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Anticancer Agents Med Chem. 2017 Mar 27. doi: 10.2174/1871520617666170327110712. [Epub ahead of print]

Post-transcriptional and Post-translational regulation of Central Carbon Metabolic Enzymes in Cancer.

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1
Division of Gastroenterology and Hepatology; Key Laboratory of Gastroenterology and Hepatology, Ministry of Health; State Key Laboratory for Oncogenes and Related Genes; Renji Hospital, School of Medicine, Shanghai Jiao Tong University; Shanghai Institute of Digestive Disease, Shanghai. China.

Abstract

Malignant transformation of cells requires specific adaptations of cellular metabolism to support growth and survival. Alterations in cancer central carbon metabolism including aerobic glycolysis, elevated glutaminolysis, dysregulated tricarboxylic acid cycle and pentose phosphate pathway, facilitating cancer development by maintaining viability and building new biomass. Although a variety of oncogenes or tumor suppressors contribute to these rewiring, accumulating evidence suggests that both post-transcriptional and post-translational modifications (PTMs) also orchestrate the tightly controlled regulation of cancer metabolic adaptations, broadening the biological mechanisms of cancer metabolic reprogramming. Micro RNA, one kind of post-transcriptional modifications, mediates transcriptional silencing of various metabolic enzymes. Additional, different kinds of PTMs play important roles in cancer metabolic rewiring by affecting the function, interaction or stability of target proteins. We survey recent studies demonstrating PTMs at lysine residues and microRNAs that are involved in reprogramming of cancer central carbon metabolism, and summarize the effect of these modifications according to different parts of central carbon metabolic pathway. Moreover, we provide an updated overview of the compounds or agents targeting central carbon metabolism in cancer. Given that the heterogeneity of cancer biology, a combination of these novel therapeutics and standard chemotherapeutic agents may obtain better benefit and overcome drug resistance. Finally, this review discusses the challenges and some new steps that may further advance this field.

KEYWORDS:

Cancer; Glutaminolysis; Glycolysis; Lysine ; Metabolism; MicroRNAs; Pentose Phosphate Pathway; Post-Translational Modifications; Tricarboxylic Acid Cycle

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