Galectin-3 Increases Gastric Cancer Cell Motility by Up-regulating Fascin-1 Expression

Background & Aims

Galectin-3 is a β-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)-3β, β-catenin, and T-cell factor (TCF) 4, and the binding of β-catenin/TCF-4 to the fascin-1 promoter. Nuclear localization of GSK-3β and β-catenin were not detected when galectin-3 was silenced. Overexpression of mutated galectin-3 (with mutations in the GSK-3β 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.

Keywords: Galectin-3, Fascin-1, Metastasis, Gastric Cancer

Abbreviations used in this paper: siRNA, small interfering RNA, GSK-3β, glycogen synthase kinase–3 beta, MMP, matrix metalloproteinase, RT-PCR, reverse-transcription polymerase chain reaction, TCF, T-cell factor