title: Beta-catenin signaling: linking renal cell carcinoma and polycystic kidney disease.
abstract: Loss of von Hippel-Lindau (VHL) tumor suppressor gene function occurs in familial and most sporadic renal cell carcinoma (RCC), resulting in the aberrant expression of genes that control cell proliferation, invasion and angiogenesis. The molecular mechanisms by which VHL loss leads to tumorigenesis are not yet fully defined. The VHL gene product, pVHL, is part of an E3 ubiquitin ligase complex that targets hypoxia inducible factors for polyubiquitination and proteosomal degradation, implicating hypoxia response genes in RCC oncogenesis. VHL loss also allows robust RCC cell invasiveness and morphogenesis in response to hepatocyte growth factor (HGF), an important regulator of kidney development and renal homeostasis. Recent elucidation of the mechanism by which pVHL represses developmental HGF responses in adult kidney has identified another oncogenically relevant E3 ligase target: beta-catenin. This discovery also further unifies recent insights into the molecular pathogenesis of polycystic kidney disease, where the identification of disease genes has revealed the integration of signaling pathways associated with primary cilia function and the regulation of cell growth and differentiation.
authors.affiliation: Urologic Oncology Branch, CCR, NCI, Bethesda, Maryland 20892-1107, USA.
authors.forename: Benedetta
authors.initials: B
authors.lastname: Peruzzi
authors.forename: Donald P
authors.initials: DP
authors.lastname: Bottaro
mesh_terms: D000818:Animals; D002292:Carcinoma, Renal Cell / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D051793:Hypoxia-Inducible Factor 1 / Q000378:metabolism; D051379:Mice; D007690:Polycystic Kidney Diseases / Q000378:metabolism* / Q000473:pathology*; D015398:Signal Transduction; D051176:beta Catenin / Q000378:metabolism*
chemical_list: D051793:Hypoxia-Inducible Factor 1; D051176:beta Catenin