ACLY and ACC1 Regulate Hypoxia-Induced Apoptosis by Modulating ETV4 via α-ketoglutarate

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During the development of most solid tumors, there are characteristic physiological differences in the tumor that result from tumor cells outgrowing their local blood supply. Two of these physiological differences, or “stresses,” that occur in the tumor are low oxygen levels (hypoxia) and an accumulation of lactic acidic (lactic acidosis). Cancer cells experiencing hypoxia and lactic acidosis tend to be more resistant to chemo- and radio-therapy and metastasize more readily. Therefore, it is important to understand how tumor cells adapt to and survive these stresses. We used a large scale screening experiment in order to find which genes and proteins are involved in tumor cell adaptation and survival under hypoxia or lactic acidosis. We found that inhibiting either of two genes involved in lipid synthesis allowed tumor cells to survive hypoxia. This occurred because silencing these genes led to an increase in the metabolite α-ketoglutarate, which repressed a transcription factor that contributed to cell death under hypoxia. This research specifically advances our understanding of how tumor cells survive hypoxia and lactic acidosis and more broadly enhances our understanding of the cellular biology of solid tumors.

Vyšlo v časopise: ACLY and ACC1 Regulate Hypoxia-Induced Apoptosis by Modulating ETV4 via α-ketoglutarate. PLoS Genet 11(10): e32767. doi:10.1371/journal.pgen.1005599
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1005599

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