title: Current views on cell metabolism in SDHx-related pheochromocytoma and paraganglioma.
abstract: Warburg's metabolic hypothesis is based on the assumption that a cancer cell's respiration must be under attack, leading to its damage, in order to obtain increased glycolysis. Although this may not apply to all cancers, there is some evidence proving that primarily abnormally functioning mitochondrial complexes are indeed related to cancer development. Thus, mutations in complex II (succinate dehydrogenase (SDH)) lead to the formation of pheochromocytoma (PHEO)/paraganglioma (PGL). Mutations in one of the SDH genes (SDHx mutations) lead to succinate accumulation associated with very low fumarate levels, increased glutaminolysis, the generation of reactive oxygen species, and pseudohypoxia. This results in significant changes in signaling pathways (many of them dependent on the stabilization of hypoxia-inducible factor), including oxidative phosphorylation, glycolysis, specific expression profiles, as well as genomic instability and increased mutability resulting in tumor development. Although there is currently no very effective therapy for SDHx-related metastatic PHEOs/PGLs, targeting their fundamental metabolic abnormalities may provide a unique opportunity for the development of novel and more effective forms of therapy for these tumors.
authors: Department of Pediatric Hematology and Oncology, 2nd Medical School, Charles University and University Hospital Motol, Prague, Czech Republic Service Central de Biophysique et de Médecine Nucléaire, CERIMED Centre Hospitalo-Universitaire Timone, Marseille, France Département d'Oncologie Moléculaire, Centre de Recherche en Cancérologie de Marseille, Marseille, France Program in Reproductive and Adult Endocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health, Building 10, CRC, 1-East, Room 1-3140, 10 Center Drive, MSC-1109, Bethesda, Maryland 20892-1109, USA.
authors: Ales
authors: A
authors: Vicha
authors: David
authors: D
authors: Taieb
authors: Karel
authors: K
authors: Pacak
mesh_terms: D000310:Adrenal Gland Neoplasms / Q000235:genetics / Q000378:metabolism*; D002468:Cell Physiological Phenomena; D006019:Glycolysis; D006801:Humans; D009154:Mutation / Q000235:genetics*; D010235:Paraganglioma / Q000235:genetics / Q000378:metabolism*; D010673:Pheochromocytoma / Q000235:genetics / Q000378:metabolism*; D013385:Succinate Dehydrogenase / Q000235:genetics*
chemical_list: D013385:Succinate Dehydrogenase
keywords: SDHx; Warburg effect; gastrointestinal stromal tumor; glycolysis; hypoxia; paraganglioma; pheochromocytoma; pseudohypoxia; reactive oxygen species; renal cell carcinoma; succinate dehydrogenase