Oncometabolites: Unconventional triggers of oncogenic signalling cascades.
Cancer is a complex and heterogeneous disease thought to be caused by multiple genetic lesions. The recent finding that enzymes of the tricarboxylic acid (TCA) cycle are mutated in cancer rekindled the hypothesis that altered metabolism might also have a role in cellular transformation. Attempts to link mitochondrial dysfunction to cancer uncovered the unexpected role of small molecule metabolites, now known as oncometabolites, in tumorigenesis. In this review, we describe how oncometabolites can contribute to tumorigenesis. We propose that lesions of oncogenes and tumour suppressors are only one of the possible routes to tumorigenesis, which include accumulation of oncometabolites triggered by environmental cues.
Medical Research Council Cancer Unit, University of Cambridge, Hutchison/MRC Research Centre, Box 197, Cambridge Biomedical Campus, Cambridge CB2 0XZ, United Kingdom.
Marco
M
Sciacovelli
Medical Research Council Cancer Unit, University of Cambridge, Hutchison/MRC Research Centre, Box 197, Cambridge Biomedical Campus, Cambridge CB2 0XZ, United Kingdom. Electronic address: cf366@MRC-CU.cam.ac.uk.
Christian
C
Frezza
D000818:Animals; D063646:Carcinogenesis; D002952:Citric Acid Cycle; D006801:Humans; D009369:Neoplasms / Q000378:metabolism*; D015398:Signal Transduction
2-Hydroxyglutarate; Cancer; FH; Fumarate; IDH; Mitochondria; Oncometabolites; SDH; Succinate