title: Transcription factor PROX1 induces colon cancer progression by promoting the transition from benign to highly dysplastic phenotype.
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.
authors.affiliation: Molecular and Cancer Biology Research Program, Biomedicum Helsinki, University of Helsinki, Haartmaninkatu 8, P.O.B. 63, 00014 Helsinki, Finland. tatiana.petrova@helsinki.fi
authors.forename: Tatiana V
authors.initials: TV
authors.lastname: Petrova
authors.forename: Antti
authors.initials: A
authors.lastname: Nykänen
authors.forename: Camilla
authors.initials: C
authors.lastname: Norrmén
authors.forename: Konstantin I
authors.initials: KI
authors.lastname: Ivanov
authors.forename: Leif C
authors.initials: LC
authors.lastname: Andersson
authors.forename: Caj
authors.initials: C
authors.lastname: Haglund
authors.forename: Pauli
authors.initials: P
authors.lastname: Puolakkainen
authors.forename: Frank
authors.initials: F
authors.lastname: Wempe
authors.forename: Harald
authors.initials: H
authors.lastname: von Melchner
authors.forename: Gérard
authors.initials: G
authors.lastname: Gradwohl
authors.forename: Sakari
authors.initials: S
authors.lastname: Vanharanta
authors.forename: Lauri A
authors.initials: LA
authors.lastname: Aaltonen
authors.forename: Juha
authors.initials: J
authors.lastname: Saharinen
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Gentile
authors.forename: Alan
authors.initials: A
authors.lastname: Clarke
authors.forename: Jussi
authors.initials: J
authors.lastname: Taipale
authors.forename: Guillermo
authors.initials: G
authors.lastname: Oliver
authors.forename: Kari
authors.initials: K
authors.lastname: Alitalo
mesh_terms: D000236:Adenoma / Q000235:genetics* / Q000473:pathology; D002278:Carcinoma in Situ / Q000235:genetics; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000235:genetics* / Q000473:pathology; D015179:Colorectal Neoplasms / Q000235:genetics; D018450:Disease Progression; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D010641:Phenotype; D025521:Tumor Suppressor Proteins / Q000235:genetics*; D051176:beta Catenin / Q000502:physiology; D000098551:Prospero-Related Homeobox 1 Protein
chemical_list: D018398:Homeodomain Proteins; D025521:Tumor Suppressor Proteins; D051176:beta Catenin; D000098551:Prospero-Related Homeobox 1 Protein