Obesity, cholesterol, and clear-cell renal cell carcinoma (RCC).
Multiple epidemiologic studies have linked the development of renal cancer to obesity. In this chapter, we begin with a review of selected population studies, followed by recent mechanistic discoveries that further link lipid deregulation to the RCC development. The upregulation of leptin and downregulation of adiponectin pathways in obesity fit well with our molecular understanding of RCC pathogenesis. In addition, two forms of hereditary RCC involve proteins, Folliculin and TRC8, that are positioned to coordinately regulate lipid and protein biosynthesis. Both of these biosynthetic pathways have important downstream consequences on HIF-1/2alpha levels and angiogenesis, key aspects in the disease pathogenesis. The role of lipid biology and its interface with protein translation regulation represents a new dimension in RCC research with potential therapeutic implications.
Drabkin
Harry A
HA
Department of Medicine and Division of Hematology-Oncology, Medical University of South Carolina, Charleston, SC, USA.
Gemmill
Robert M
RM
D052242:Adiponectin / Q000378:metabolism; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism; D002292:Carcinoma, Renal Cell / Q000209:etiology* / Q000235:genetics / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D002784:Cholesterol / Q000378:metabolism*; D003598:Cytoskeletal Proteins; D004970:Estrone / Q000378:metabolism; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000378:metabolism; D007680:Kidney Neoplasms / Q000209:etiology* / Q000235:genetics / Q000378:metabolism; D020738:Leptin / Q000378:metabolism; D008055:Lipids / Q000096:biosynthesis / Q000235:genetics; D018832:Molecular Chaperones; D009386:Neoplastic Syndromes, Hereditary / Q000453:epidemiology / Q000235:genetics / Q000378:metabolism; D009765:Obesity / Q000150:complications* / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism; D051779:Sterol Regulatory Element Binding Proteins / Q000378:metabolism; D000099162:Endothelial PAS Domain-Containing Protein 1
D052242:Adiponectin; D051792:Basic Helix-Loop-Helix Proteins; D002352:Carrier Proteins; D002784:Cholesterol; D003598:Cytoskeletal Proteins; D004970:Estrone; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D020738:Leptin; D008055:Lipids; D018832:Molecular Chaperones; D011956:Receptors, Cell Surface; D051779:Sterol Regulatory Element Binding Proteins; D000099162:Endothelial PAS Domain-Containing Protein 1; C497442:HIF1A protein, human; C114025:RNF139 protein, human; C108825:VBP1 protein, human