title: Overexpression of a key regulator of lipid homeostasis, Scap, promotes respiration in prostate cancer cells.
abstract: Prostate metabolism is unique, characterised by cholesterol accumulation and reduced respiration. Are these related? We modulated cholesterol levels and despite changes in mitochondrial cholesterol content, we saw no effects on lactate production or respiration. Instead, these features may be related via sterol regulatory element-binding protein 2 (SREBP-2), the master transcriptional regulator of cholesterol synthesis. SREBP-2 diverts acetyl-CoA into cholesterol synthesis and may thus reduce respiration. We examined LNCaP cells overexpressing the SREBP-2 regulator, Scap: although having higher SREBP-2 activity, these cells displayed higher respiration. This striking observation warrants further investigation. Given that SREBP-2 and Scap are regulated by factors driving prostate growth, exploring this observation further could shed light on prostate carcinogenesis.
authors: School of Biotechnology and Biomolecular Sciences, The University of New South Wales, Sydney 2052, Australia.
authors: Anika Vinayak
authors: AV
authors: Prabhu
authors: James Robert
authors: JR
authors: Krycer
authors: Andrew John
authors: AJ
authors: Brown
mesh_terms: D000818:Animals; D016466:CHO Cells; D045744:Cell Line, Tumor; D002784:Cholesterol / Q000378:metabolism; D006224:Cricetinae; D003412:Cricetulus; D015972:Gene Expression Regulation, Neoplastic; D006706:Homeostasis / Q000235:genetics; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D007773:Lactates / Q000378:metabolism; D050356:Lipid Metabolism; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D010101:Oxygen Consumption; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051782:Sterol Regulatory Element Binding Protein 2 / Q000235:genetics / Q000378:metabolism*
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D007773:Lactates; D008565:Membrane Proteins; C497390:SREBF2 protein, human; C102196:SREBP cleavage-activating protein; D051782:Sterol Regulatory Element Binding Protein 2; D002784:Cholesterol