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

被引：162

作者：

Petrova, Tatiana V. ^{[10
]}

Nykanen, Antti ^{[10
]}

Norrmen, Camilla ^{[10
]}

Ivanov, Konstantin I. ^{[10
]}

Andersson, Leif C. ^{[2
]}

Haglund, Caj ^{[3
]}

Puolakkainen, Pauli ^{[3
]}

Wempe, Frank ^{[4
]}

von Melchner, Harald ^{[4
]}

Gradwohl, Gerard ^{[5
]}

Vanharanta, Sakari ^{[6
]}

Aaltonen, Lauri A. ^{[6
]}

Saharinen, Juha ^{[7
]}

Gentile, Massimiliano ^{[7
]}

Clarke, Alan ^{[8
]}

Taipale, Jussi ^{[6
]}

Oliver, Guillermo ^{[9
]}

Alitalo, Kari ^{[1
,10
]}

机构：

[1] Helsinki Univ Hosp, Ludwig Inst Canc Res, Helsinki, Finland

[2] Univ Helsinki, Dept Pathol, Haartman Inst, FIN-00014 Helsinki, Finland

[3] Univ Helsinki, Cent Hosp, Dept Surg, Helsinki 00029, Finland

[4] Goethe Univ Frankfurt, Sch Med, Lab Mol Hematol, D-60590 Frankfurt, Germany

[5] CNRS, INSERM, UMR 7104,U596, Dept Cell & Dev Biol,Inst Genet & Biol Mol & Cell, F-67404 Illkirch Graffenstaden, France

[6] Univ Helsinki, Genome Scale Biol Res Program, Biomedicum Helsinki, FIN-00014 Helsinki, Finland

[7] Univ Helsinki, Genome Informat Unit, Biomedicum Helsinki, FIN-00014 Helsinki, Finland

[8] Cardiff Univ, Cardiff Sch Biosci, Cardiff CF10 3US, Wales

[9] St Jude Childrens Res Hosp, Dept Genet & Tumor Cell Biol, Memphis, TN 38105 USA

[10] Univ Helsinki, Mol & Canc Biol Res Program, Biomedicum Helsinki, FIN-00014 Helsinki, Finland

来源：

CANCER CELL | 2008年 / 13卷 / 05期

基金：

英国医学研究理事会;

关键词：

D O I：

10.1016/j.ccr.2008.02.020

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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.

引用

页码：407 / 419

页数：13

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