title: Oct1 loss of function induces a coordinate metabolic shift that opposes tumorigenicity.
abstract: Cancer cells frequently undergo a shift from oxidative to glycolytic metabolism. Although there is interest in targeting metabolism as a form of cancer therapy, this area still remains in its infancy. Using cells, embryos and adult animals, we show here that loss of the widely expressed transcription factor Oct1 induces a coordinated metabolic shift: mitochondrial activity and amino acid oxidation are increased, while glucose metabolism is reduced. Altered expression of direct Oct1 targets encoding metabolic regulators provides a mechanistic underpinning to these results. We show that these metabolic changes directly oppose tumorigenicity. Collectively, our findings show that Oct1, the genes it regulates and the pathways these genes affect could be used as targets for new modes of cancer therapy.
authors.affiliation: Department of Pathology, University of Utah School of Medicine, Salt Lake City, Utah 84112, USA.
authors.forename: Arvind
authors.initials: A
authors.lastname: Shakya
authors.forename: Robert
authors.initials: R
authors.lastname: Cooksey
authors.forename: James E
authors.initials: JE
authors.lastname: Cox
authors.forename: Victoria
authors.initials: V
authors.lastname: Wang
authors.forename: Donald A
authors.initials: DA
authors.lastname: McClain
authors.forename: Dean
authors.initials: D
authors.lastname: Tantin
mesh_terms: D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D004622:Embryo, Mammalian / Q000166:cytology / Q000378:metabolism / Q000648:ultrastructure; D005347:Fibroblasts / Q000378:metabolism / Q000648:ultrastructure; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D005947:Glucose / Q000378:metabolism; D006019:Glycolysis; D006801:Humans; D055442:Metabolome; D051379:Mice; D008928:Mitochondria / Q000378:metabolism; D009369:Neoplasms / Q000378:metabolism* / Q000473:pathology*; D050811:Octamer Transcription Factor-1 / Q000172:deficiency* / Q000378:metabolism; D010084:Oxidation-Reduction
chemical_list: D000596:Amino Acids; D050811:Octamer Transcription Factor-1; D005947:Glucose