Thrombospondin-1 is a matricellular protein with potent antitumour activities, the levels of which determine the fate of many different tumours, including renal carcinomas.
However, the factors that regulate this protein remain unclear. In renal carcinomas, hypoxic conditions enhance the expression of angiogenic factors that help adapt tumour cells to their hostile environment. Therefore, we hypothesized that anti-angiogenic factors should correspondingly be dampened. Indeed, we found that hypoxia decreased the thrombospondin-1 protein in several clear cell renal carcinoma cell lines (ccRCC), although no transcriptional regulation was observed. Furthermore, we proved that hypoxia stimulates multiple signals that independently contribute to diminish thrombospondin-1 in ccRCC, which include a decrease in the activity of oxygen-dependent prolylhydroxylases (PHDs) and activation of the PI3K/Akt signalling pathway. In addition, thrombospondin-1 regulation in hypoxia proved to be important for ccRCC cell migration and invasion.
Written by:
Bienes-Martínez R, Ordóñez A, Feijoo-Cuaresma M, Corral-Escariz M, Mateo G, Stenina O, Jiménez B, Calzada MJ. Are you the author?
Instituto de Investigación Sanitaria Princesa, Department of Medicine, Universidad Autónoma of Madrid, Madrid, Spain.
Reference: Sci Rep. 2012;2:788.
doi: 10.1038/srep00788
PubMed Abstract
PMID: 23145312
UroToday.com Investigative Urology Section
