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Variable FZD7 expression in colorectal cancers indicates regulation by the tumour microenvironment
Author(s) -
Vincan Elizabeth,
Flanagan Dustin J.,
Pouliot Normand,
Brabletz Thomas,
Spaderna Simone
Publication year - 2010
Publication title -
developmental dynamics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.634
H-Index - 141
eISSN - 1097-0177
pISSN - 1058-8388
DOI - 10.1002/dvdy.22045
Subject(s) - wnt signaling pathway , biology , colorectal cancer , fibronectin , extracellular matrix , cancer research , catenin , population , tumor microenvironment , frizzled , beta catenin , cancer , microbiology and biotechnology , gene , genetics , medicine , environmental health
Abstract Recent evidence shows that a sub‐population of Wnt/β‐catenin target genes is specifically induced in different tissue contexts. FZD7 is a putative Wnt/β‐catenin target gene and although it is highly expressed in well‐differentiated colorectal cancer tumour cells, its expression is decreased in de‐differentiated tumour cells at the invasive front despite elevated Wnt/β‐catenin signalling in this area. This variable expression of FZD7 implicates additional regulation by the microenvironment; however, this has not been investigated. To begin to elucidate the role of extracellular matrix in regulating FZD7 expression, we generated a FZD7 promoter reporter and analysed FZD7 promoter activity in colorectal cancer cells grown on different matrices. We demonstrate that the FZD7 promoter is regulated by β‐catenin in colorectal cancer cells and observed decreased promoter activity in cells grown on fibronectin but not collagen I or collagen IV. Thus, expression of FZD7 in colorectal cancer may be regulated by fibronectin in the microenvironment. Developmental Dynamics 239:311–317, 2010. © 2009 Wiley‐Liss, Inc.