Transcription factor PROX1 induces colon cancer progression by promoting the transition from benign to highly dysplastic phenotype. - Archive ouverte HAL Access content directly
Journal Articles Cancer Cell Year : 2008

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

Tatiana V Petrova
  • Function : Author
Antti Nykänen
  • Function : Author
Camilla Norrmén
  • Function : Author
Konstantin I Ivanov
  • Function : Author
Leif C Andersson
  • Function : Author
Caj Haglund
  • Function : Author
Pauli Puolakkainen
  • Function : Author
Frank Wempe
  • Function : Author
Harald von Melchner
  • Function : Author
Sakari Vanharanta
  • Function : Author
Lauri A Aaltonen
  • Function : Author
Juha Saharinen
  • Function : Author
Massimiliano Gentile
  • Function : Author
Alan Clarke
  • Function : Author
Jussi Taipale
  • Function : Author
Guillermo Oliver
  • Function : Author
Kari Alitalo
  • Function : Author

Abstract

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.

Dates and versions

hal-00282904 , version 1 (28-05-2008)

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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⟩
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