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Regulation of tumor metabolism by post translational modifications on metabolic enzymes

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CANCER GENE THERAPY
卷 30, 期 4, 页码 548-558

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DOI: 10.1038/s41417-022-00521-x

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Metabolic reprogramming is a characteristic of cancer development and metastasis, which involves the modulation of multiple metabolic pathways to support cancer cell growth. The activity of rate-limiting enzymes in these pathways is specifically regulated through transcriptional, translational, and post translational modifications to maintain enhanced activity.
Metabolic reprogramming is a hallmark of cancer development, progression, and metastasis. Several metabolic pathways such as glycolysis, tricarboxylic acid (TCA) cycle, lipid metabolism, and glutamine catabolism are frequently altered to support cancer growth. Importantly, the activity of the rate-limiting metabolic enzymes in these pathways are specifically modulated in cancer cells. This is achieved by transcriptional, translational, and post translational regulations that enhance the expression, activity, stability, and substrate sensitivity of the rate-limiting enzymes. These mechanisms allow the enzymes to retain increased activity supporting the metabolic needs of rapidly growing tumors, sustain their survival in the hostile tumor microenvironments and in the metastatic lesions. In this review, we primarily focused on the post translational modifications of the rate-limiting enzymes in the glucose and glutamine metabolism, TCA cycle, and fatty acid metabolism promoting tumor progression and metastasis.

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