Variable FZD7 expression in colorectal cancers indicates regulation by the tumour microenvironment.
Recent evidence shows that a sub-population of Wnt/beta-catenin target genes is specifically induced in different tissue contexts. FZD7 is a putative Wnt/beta-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/beta-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 beta-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.
Vincan
Elizabeth
E
Cancer Biology Laboratory, Department of Anatomy and Cell Biology, University of Melbourne, Australia. evincan@unimelb.edu.au
Flanagan
Dustin J
DJ
Pouliot
Normand
N
Brabletz
Thomas
T
Spaderna
Simone
S
D003094:Collagen / Q000378:metabolism*; D015179:Colorectal Neoplasms / Q000378:metabolism*; D003470:Culture Media / Q000737:chemistry / Q000378:metabolism*; D017931:DNA Primers / Q000235:genetics; D005109:Extracellular Matrix; D005353:Fibronectins / Q000378:metabolism*; D051157:Frizzled Receptors / Q000235:genetics / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics / Q000502:physiology*; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D011401:Promoter Regions, Genetic / Q000235:genetics; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured; D051176:beta Catenin / Q000378:metabolism*
D003470:Culture Media; D017931:DNA Primers; C115810:FZD7 protein, human; D005353:Fibronectins; D051157:Frizzled Receptors; D043562:Receptors, G-Protein-Coupled; D051176:beta Catenin; D003094:Collagen