Abstract 1272: Role of c-Myc, Oct1 and KLF4 in cell metabolism: Involvement of pluripotency factors in metabolic remodeling during tumorigenesis

Abstract

Abstract Embryonic stem cells have the ability to give rise to different cell types and also the self reniewal capacity. Those features are essentially controlled by pluripotency factors which maintain cells into an undifferentiated state. Cancer cells are distinguished from normal cells by a dedifferentiation process in which the expression of pluripotency factors can be increased. c-Myc, Oct4 and KLF4 are pluripotency transcription factors. Oct-1, homologue of Oct-4, have been recently revealed to be pro-tumorigenic and his expression, such as c-Myc, is increased in various cancers. In this study, we investigated the role of this transcription factors into the cell metabolism. The role of the oncogene MYC on tumor cell metabolism has been largely studied. In cancer cells, c-Myc induces the expression of genes involved in glycolysis and glutaminolysis. However, the entire metabolic changes induced by c-Myc have not yet been elucidated. Furthermore, little is known about the role of Oct-1 and KLF4 in cancer metabolism. We have used the metabolic footprinting approach in order to characterize the Oct-1, c-Myc and KLF4 deficient cells and to identify the induced consecutive metabolic remodeling. Because of the variability of mutations observed in cancer cells, we investigated the effects induced by Oct-1, KLF4 and c-Myc deficiencies in mouse and rat embryonic fibroblasts by using UPLC (Ultra performance liquid chromatography). The uptake and release of metabolites was quantified by providing different substrates (glutamine or fatty acid). The glucose consumption and the lactate production which defined as the Warburg effect was measured. The mitochondrial function was investigated by oxygen consumption rate measurement. We found that the metabolites produced by Oct-1, KLF4 and c-Myc deficient cells seems to present a signature which can explain there over-expression in tumors. Our results suggest that embryonic stem cells related pluripotency transcription factors are implicated into the metabolic remodeling of cancer cells. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1272. doi:10.1158/1538-7445.AM2011-1272