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. 2010 Mar;138(3):1035-45.e1-2.
doi: 10.1053/j.gastro.2009.09.061. Epub 2009 Oct 8.

Galectin-3 Increases Gastric Cancer Cell Motility by Up-Regulating fascin-1 Expression

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Galectin-3 Increases Gastric Cancer Cell Motility by Up-Regulating fascin-1 Expression

Seok-Jun Kim et al. Gastroenterology. .

Abstract

Background & aims: Galectin-3 is a beta-galactoside-binding protein that increases gastric cancer cell motility in response to integrin signaling and is highly expressed in gastric tumor cells. Galectin-3 induces cytoskeletal remodeling to increase cell motility, but the mechanisms of this process are not understood. We investigated the effects of galectin-3 on fascin-1, an actin-bundling protein.

Methods: We collected malignant and normal tissues from gastric cancer patients and examined the expression levels of galectin-3 and fascin-1. We silenced galectin-3 expression in human gastric cancer cell lines using small interfering RNA and lenti-viral constructs and determined the effects on fascin-1 expression, cell motility, and invasion.

Results: Malignant gastric tissues expressed high levels of galectin-3 and fascin-1, compared with normal gastric tissues. Silencing of galectin-3 resulted in altered cancer cell morphology, reduced fascin-1 expression, decreased cell motility, and reduced malignant cell invasion. Galectin-3 overexpression reversed these effects. Silencing of fascin-1 also reduced cell motility and caused changes in cell shape, as did silencing of galectin-3. Furthermore, galectin-3 silencing inhibited the interaction between glycogen synthase kinase (GSK)-3beta, beta-catenin, and T-cell factor (TCF) 4, and the binding of beta-catenin/TCF-4 to the fascin-1 promoter. Nuclear localization of GSK-3beta and beta-catenin were not detected when galectin-3 was silenced. Overexpression of mutated galectin-3 (with mutations in the GSK-3beta binding and phosphorylation motifs) did not increase fascin-1 levels, in contrast to overexpression of wild-type galectin-3.

Conclusions: Galectin-3 increases cell motility by up-regulating fascin-1 expression. Galectin-3 might be a potential therapeutic target for the prevention and treatment of gastric cancer progression.

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