title: Autocrine stimulation of clear-cell renal carcinoma cell migration in hypoxia via HIF-independent suppression of thrombospondin-1.
abstract: 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.
authors.affiliation: Instituto de Investigación Sanitaria Princesa, Department of Medicine, Universidad Autónoma of Madrid, Madrid, Spain.
authors.forename: Raquel
authors.initials: R
authors.lastname: Bienes-Martínez
authors.forename: Angel
authors.initials: A
authors.lastname: Ordóñez
authors.forename: Mónica
authors.initials: M
authors.lastname: Feijoo-Cuaresma
authors.forename: María
authors.initials: M
authors.lastname: Corral-Escariz
authors.forename: Gloria
authors.initials: G
authors.lastname: Mateo
authors.forename: Olga
authors.initials: O
authors.lastname: Stenina
authors.forename: Benilde
authors.initials: B
authors.lastname: Jiménez
authors.forename: María J
authors.initials: MJ
authors.lastname: Calzada
mesh_terms: D019898:Autocrine Communication; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism; D002292:Carcinoma, Renal Cell / Q000235:genetics / Q000378:metabolism; D015687:Cell Hypoxia; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D006801:Humans; D053858:Metabolic Networks and Pathways; D009361:Neoplasm Invasiveness / Q000235:genetics; D051058:Oncogene Protein v-akt / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D019700:Thrombospondin 1 / Q000235:genetics / Q000378:metabolism; D000099162:Endothelial PAS Domain-Containing Protein 1
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D051058:Oncogene Protein v-akt; D019869:Phosphatidylinositol 3-Kinases; D019700:Thrombospondin 1; D000099162:Endothelial PAS Domain-Containing Protein 1