Malic enzyme 1 (ME1) in the biology of cancer: it is not just intermediary metabolism
| Autor: | Frank A. Simmen, Rosalia C. M. Simmen, Iad Alhallak |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Epithelial-Mesenchymal Transition Malic enzyme Adipose tissue 030209 endocrinology & metabolism Biology medicine.disease_cause Article 03 medical and health sciences 0302 clinical medicine Endocrinology Mediator Malate Dehydrogenase Neoplasms Gene expression medicine Animals Humans Molecular Biology Lipid Metabolism In vitro Cell biology Oxidative Stress 030104 developmental biology Disease Susceptibility Thioredoxin Carcinogenesis Energy Metabolism Oxidation-Reduction Oxidative stress |
| Zdroj: | J Mol Endocrinol |
| ISSN: | 1479-6813 |
| Popis: | Malic enzyme 1 (ME1) is a cytosolic protein that catalyzes the conversion of malate to pyruvate while concomitantly generating NADPH from NADP. Early studies identified ME1 as a mediator of intermediary metabolism primarily through its participatory roles in lipid and cholesterol biosynthesis. ME1 was one of the first identified insulin-regulated genes in liver and adipose and is a transcriptional target of thyroxine. Multiple studies have since documented that ME1 is pro-oncogenic in numerous epithelial cancers. In tumor cells, the reduction of ME1 gene expression or the inhibition of its activity resulted in decreases in proliferation, epithelial-to-mesenchymal transition and in vitro migration, and conversely, in promotion of oxidative stress, apoptosis and/or cellular senescence. Here, we integrate recent findings to highlight ME1’s role in oncogenesis, provide a rationale for its nexus with metabolic syndrome and diabetes, and raise the prospects of targeting the cytosolic NADPH network to improve therapeutic approaches against multiple cancers. |
| Databáze: | OpenAIRE |
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