BackgroundGalectin-3 is known to regulate cancer metastasis.However, the underlying mechanism has not been defined.Through the DNA microarray studies after galectin-3 silencing, we demonstrated here that galectin-3 plays a key role in up-regulating the expressions of protease-activated receptor-1 (PAR-1) and matrix metalloproteinase-1 (MMP-1) PAR-1 thereby promoting gastric satisfyer pro penguin next generation cancer metastasis.Methodology/principal findingsWe examined the expression levels of Galectin-3, PAR-1, and MMP-1 in gastric cancer patient tissues and also the effects of silencing these proteins with specific siRNAs and of over-expressing them using specific lenti-viral constructs.We also employed zebrafish embryo model for analysis of in vivo gastric cancer cell invasion.
These studies demonstrated that: a) galectin-3 silencing decreases the expression of PAR-1.b) galectin-3 over-expression increases cell migration and invasion and this increase can be reversed by PAR-1 silencing, indicating that galectin-3 increases cell migration and invasion via PAR-1 up-regulation.c) galectin-3 directly interacts with AP-1 transcriptional factor, and this complex binds to PAR-1 promoter and drives PAR-1 transcription.d) galectin-3 also amplifies phospho-paxillin, a PAR-1 downstream target, by increasing MMP-1 expression.MMP-1 silencing blocks phospho-paxillin amplification and cell invasion caused by galectin-3 over-expression.
e) Silencing of either galectin-3, PAR-1 or MMP-1 significantly reduced cell migration into the vessels in zebrafish embryo model.f) Galectin-3, PAR-1, and MMP-1 are highly expressed and co-localized in malignant tissues from gastric cancer patients.Conclusions/significanceGalectin-3 plays the key role of activating cell surface receptor through production of protease and boosts gastric cancer metastasis.Galectin-3 has the potential to serve as a useful pharmacological target for here prevention of gastric cancer metastasis.