Fascin, an actin-bundling protein, modulates colonic epithelial cell invasiveness and differentiation in vitro.
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.
Jawhari
Aida U
AU
Digestive Diseases Research Center, St. Bartholomew's and The Royal London School of Medicine and Dentistry, London.
Buda
Andrea
A
Jenkins
Michelle
M
Shehzad
Khurram
K
Sarraf
Catherine
C
Noda
Masao
M
Farthing
Michael J G
MJ
Pignatelli
Massimo
M
Adams
Josephine C
JC
D000199:Actins / Q000378:metabolism; D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology; D015820:Cadherins / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation / Q000235:genetics; D002455:Cell Division; D002465:Cell Movement / Q000235:genetics; D002478:Cells, Cultured; D024042:Collagen Type I / Q000378:metabolism; D024141:Collagen Type IV / Q000378:metabolism; D003106:Colon / Q000166:cytology; D003110:Colonic Neoplasms / Q000378:metabolism* / Q000473:pathology; D003598:Cytoskeletal Proteins / Q000378:metabolism; D004847:Epithelial Cells / Q000166:cytology / Q000502:physiology; D015870:Gene Expression; D006801:Humans; D019012:Integrin beta1 / Q000378:metabolism; D007413:Intestinal Mucosa / Q000166:cytology / Q000378:metabolism; D007797:Laminin / Q000378:metabolism; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism*; D009361:Neoplasm Invasiveness / Q000235:genetics; D014162:Transfection; D014407:Tumor Cells, Cultured; D015854:Up-Regulation
D000199:Actins; D015820:Cadherins; D002352:Carrier Proteins; D024042:Collagen Type I; D024141:Collagen Type IV; D003598:Cytoskeletal Proteins; D019012:Integrin beta1; D007797:Laminin; D008840:Microfilament Proteins; C121346:laminin 1; C020324:fascin