Fascin, an actin-bundling protein, modulates colonic epithelial cell invasiveness and differentiation in vitro

Aida U. Jawhari, Andrea Buda, Michelle Jenkins, Khurram Shehzad, Catherine Sarraf, Masao Noda, Michael J G Farthing, Massimo Pignatelli, Josephine C. Adams

Research output: Contribution to journalArticle

169 Citations (Scopus)

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 phe notype in colonic carcinoma.

Original languageEnglish
Pages (from-to)69-80
Number of pages12
JournalAmerican Journal of Pathology
Volume162
Issue number1
Publication statusPublished - Jan 1 2003
Externally publishedYes

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Actins
Cell Differentiation
Epithelial Cells
Cell Surface Extensions
Cell Movement
Proteins
Adhesives
Epithelium
Focal Adhesions
Actin Cytoskeleton
Cell Communication
Neoplasms
Adenocarcinoma
Up-Regulation
Collagen
Cell Culture Techniques
Gels
fascin
In Vitro Techniques
Neoplasm Metastasis

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Jawhari, A. U., Buda, A., Jenkins, M., Shehzad, K., Sarraf, C., Noda, M., ... Adams, J. C. (2003). Fascin, an actin-bundling protein, modulates colonic epithelial cell invasiveness and differentiation in vitro. American Journal of Pathology, 162(1), 69-80.

Fascin, an actin-bundling protein, modulates colonic epithelial cell invasiveness and differentiation in vitro. / Jawhari, Aida U.; Buda, Andrea; Jenkins, Michelle; Shehzad, Khurram; Sarraf, Catherine; Noda, Masao; Farthing, Michael J G; Pignatelli, Massimo; Adams, Josephine C.

In: American Journal of Pathology, Vol. 162, No. 1, 01.01.2003, p. 69-80.

Research output: Contribution to journalArticle

Jawhari, AU, Buda, A, Jenkins, M, Shehzad, K, Sarraf, C, Noda, M, Farthing, MJG, Pignatelli, M & Adams, JC 2003, 'Fascin, an actin-bundling protein, modulates colonic epithelial cell invasiveness and differentiation in vitro', American Journal of Pathology, vol. 162, no. 1, pp. 69-80.
Jawhari AU, Buda A, Jenkins M, Shehzad K, Sarraf C, Noda M et al. Fascin, an actin-bundling protein, modulates colonic epithelial cell invasiveness and differentiation in vitro. American Journal of Pathology. 2003 Jan 1;162(1):69-80.
Jawhari, Aida U. ; Buda, Andrea ; Jenkins, Michelle ; Shehzad, Khurram ; Sarraf, Catherine ; Noda, Masao ; Farthing, Michael J G ; Pignatelli, Massimo ; Adams, Josephine C. / Fascin, an actin-bundling protein, modulates colonic epithelial cell invasiveness and differentiation in vitro. In: American Journal of Pathology. 2003 ; Vol. 162, No. 1. pp. 69-80.
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