Novel insights into the role of the tumor suppressor von Hippel Lindau in cellular differentiation, ciliary biology, and cyst repression.
The growth and differentiation of renal tubular epithelial cells is normally tightly controlled. Disturbances can lead to the development of renal cysts or renal cell carcinomas, clinically relevant disease entities, which have so far been considered as being caused by entirely distinct mechanisms. Clear cell renal carcinoma, the most frequent type of renal cancer is associated with inactivation of the von Hippel Lindau (VHL) protein. Genetic defects leading to cystic kidney disease usually affect proteins that play a role in structure or function of primary cilia of renal epithelial cells. Accumulating evidence suggests that the VHL protein also controls cilia function and that its inactivation may result in both malignant or nonmalignant growth of epithelial cells and that this effect is in part mediated through the accumulation of hypoxia-inducible factors. Unraveling the complex role of VHL in renal epithelial cells is likely to shed further insight into mechanism of epithelial growth control, epithelial-mesenchymal transformation, and tumor development.
Wiesener
Michael S
MS
Department of Nephrology and Hypertension, University of Erlangen-Nuremberg, Erlangen, Germany. michael.wiesener@uk-erlangen.de
Maxwell
Patrick H
PH
Eckardt
Kai-Uwe
KU
D002292:Carcinoma, Renal Cell / Q000209:etiology / Q000473:pathology; D002454:Cell Differentiation; D002923:Cilia / Q000473:pathology; D006801:Humans; D007668:Kidney / Q000737:chemistry / Q000166:cytology* / Q000473:pathology; D052177:Kidney Diseases, Cystic / Q000209:etiology; D051794:Von Hippel-Lindau Tumor Suppressor Protein / Q000502:physiology*
D051794:Von Hippel-Lindau Tumor Suppressor Protein