Transcription factor PROX1 induces colon cancer progression by promoting the transition from benign to highly dysplastic phenotype.

Tatiana V Petrova , Antti Nykänen , Camilla Norrmén , Konstantin I Ivanov , Leif C Andersson , Caj Haglund , Pauli Puolakkainen , Frank Wempe , Harald von Melchner , Gérard Gradwohl (1) , Sakari Vanharanta , Lauri A Aaltonen , Juha Saharinen , Massimiliano Gentile , Alan Clarke , Jussi Taipale , Guillermo Oliver , Kari Alitalo

1 IGBMC - Institut de génétique et biologie moléculaire et cellulaire

The Drosophila transcription factor Prospero functions as a tumor suppressor, and it has been suggested that the human counterpart of Prospero, PROX1, acts similarly in human cancers. However, we show here that PROX1 promotes dysplasia in colonic adenomas and colorectal cancer progression. PROX1 expression marks the transition from benign colon adenoma to carcinoma in situ, and its loss inhibits growth of human colorectal tumor xenografts and intestinal adenomas in Apc(min/+) mice, while its transgenic overexpression promotes colorectal tumorigenesis. Furthermore, in intestinal tumors PROX1 is a direct and dose-dependent target of the beta-catenin/TCF signaling pathway, responsible for the neoplastic transformation. Our data underscore the complexity of cancer pathogenesis and implicate PROX1 in malignant tumor progression through the regulation of cell polarity and adhesion.

Domaines: Biologie moléculaire

Tatiana V Petrova, Antti Nykänen, Camilla Norrmén, Konstantin I Ivanov, Leif C Andersson, et al.. Transcription factor PROX1 induces colon cancer progression by promoting the transition from benign to highly dysplastic phenotype.. Cancer Cell, 2008, 13 (5), pp.407-19. ⟨10.1016/j.ccr.2008.02.020⟩. ⟨hal-00282904⟩