Frizzled-7 receptor ectodomain expression in a colon cancer cell line induces morphological change and attenuates tumor growth.
Frizzled (FZD) receptors have a conserved N-terminal extracellular cysteine-rich domain that interacts with Wnts and co-expression of the receptor ectodomain can antagonize FZD-mediated signalling. Using the ectodomain as an antagonist we have modulated endogenous FZD7 signalling in the moderately differentiated colon adenocarcinoma cell line, SK-CO-1. Unlike the parental cell line, which grows as tightly associated adherent cell clusters, the FZD7 ectodomain expressing cells display a spread out morphology and grow as a monolayer in tissue culture. This transition in morphology was associated with decreased levels of plasma membrane-associated E-cadherin and beta-catenin, localized increased levels of vimentin and redistribution of alpha6 integrin to cellular processes in the FZD7 ectodomain expressing cells. The morphological and phenotype changes induced by FZD7 ectodomain expression in SK-CO-1 cells is thus consistent with the cells undergoing an epithelial-to-mesenchymal-like transition. Furthermore, initiation of tumor formation in a xenograft tumor growth assay was attenuated in the FZD7 ectodomain expressing cells. Our results indicate a pivotal role for endogenous FZD7 in morphology transitions that are associated with colon tumor initiation and progression.
Vincan
Elizabeth
E
Research Division, Peter MacCallum Cancer Centre, 1 St. Andrew's Place, East Melbourne, Vic. 3002, Australia. Elizabeth.Vincan@petermac.org
Darcy
Phillip K
PK
Smyth
Mark J
MJ
Thompson
Erik W
EW
Thomas
Robert J S
RJ
Phillips
Wayne A
WA
Ramsay
Robert G
RG
D000230:Adenocarcinoma / Q000737:chemistry / Q000378:metabolism / Q000473:pathology*; D000818:Animals; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000737:chemistry / Q000378:metabolism / Q000473:pathology*; D051157:Frizzled Receptors; D015870:Gene Expression; D006801:Humans; D039503:Integrin alpha6 / Q000032:analysis / Q000378:metabolism; D051379:Mice; D016513:Mice, SCID; D017434:Protein Structure, Tertiary; D043562:Receptors, G-Protein-Coupled / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D023041:Xenograft Model Antitumor Assays
C115810:FZD7 protein, human; D051157:Frizzled Receptors; D039503:Integrin alpha6; D043562:Receptors, G-Protein-Coupled