RRC ID 73065
Author Jawhari AU, Buda A, Jenkins M, Shehzad K, Sarraf C, Noda M, Farthing MJ, Pignatelli M, Adams JC.
Title Fascin, an actin-bundling protein, modulates colonic epithelial cell invasiveness and differentiation in vitro.
Journal Am J Pathol
Abstract In epithelial tissue, cell-matrix and cell-cell adhesive interactions have important roles in the normal organization and stabilization of the cell layer. The malignant conversion of epithelial cells involves alterations in the expression and function of these adhesion systems that enable a switch to a migratory phenotype in tumor invasion and metastasis. Fascin is an actin-crosslinking protein that is found in the core actin bundles of cell-surface spikes and projections that are implicated in cell motility. We demonstrate that fascin is not detectable in normal colonic epithelium, but is dramatically up-regulated in colorectal adenocarcinoma. To test the hypothesis that fascin could participate in tumor invasive behavior, we developed a cell culture model to examine the effect of fascin expression on the adhesive interactions, invasiveness, and differentiation of colonic epithelial cells. We report marked effects on the organization of cell-surface protrusions, actin cytoskeleton, and focal adhesions in the absence of alterations in the protein levels of the major components of these structures. These effects correlate with alterations in cell movements on two-dimensional matrix, and increased invasiveness in three-dimensional matrix. The cells also show increased proliferation and decreased capacity for normal glandular differentiation in collagen gels. We propose that up-regulation of fascin, by promoting the formation of protrusive, actin-based, cell-motility structures, could be a significant component in the acquisition of invasive phenotype in colonic carcinoma.
Volume 162(1)
Pages 69-80
Published 2003-1-1
DOI 10.1016/S0002-9440(10)63799-6
PII S0002-9440(10)63799-6
PMID 12507891
PMC PMC1851132
MeSH Actins / metabolism Adenocarcinoma / metabolism* Adenocarcinoma / pathology Cadherins / metabolism Carrier Proteins / genetics Carrier Proteins / metabolism* Cell Differentiation / genetics Cell Division Cell Movement / genetics Cells, Cultured Collagen Type I / metabolism Collagen Type IV / metabolism Colon / cytology Colonic Neoplasms / metabolism* Colonic Neoplasms / pathology Cytoskeletal Proteins / metabolism Epithelial Cells* / cytology Epithelial Cells* / physiology Gene Expression Humans Integrin beta1 / metabolism Intestinal Mucosa / cytology Intestinal Mucosa / metabolism Laminin / metabolism Microfilament Proteins / genetics Microfilament Proteins / metabolism* Neoplasm Invasiveness / genetics Transfection Tumor Cells, Cultured Up-Regulation
IF 3.491
Human and Animal Cells MKN7(RCB0999) MKN45(RCB1001)