The promigratory activity of the matricellular protein galectin-3 depends on the activation of PI-3 kinase

Expression of Galectin-3 is associated with sarcoma progression, invasion and metastasis. Here we determined the role of extracellular Galectin-3 on migration of sarcoma cells on laminin-111. Cell lines from methylcholanthrene-induced sarcomas from both wild type and Galectin-3(-/-) mice were established. Despite the presence of similar levels of laminin-binding integrins on the cell surface, Galectin-3(-/-) sarcoma cells were more adherent and less migratory than Galectin-3(+/+) sarcoma cells on laminin-111. When Galectin-3 was transiently expressed in Galectin-3(-/-) sarcoma cells, it inhibited cell adhesion and stimulated the migratory response to laminin in a carbohydrate-dependent manner. Extracellular Galectin-3 led to the recruitment of SHP-2 Phosphatase to focal adhesion plaques, followed by a decrease in the amount of phosphorylated FAK and phospho-paxillin in the lamellipodia of migrating cells. The promigratory activity of extracellular Galectin-3 was inhibitable by wortmannin, implicating the activation of a PI-3 kinase dependent pathway in the Galectin-3 triggered disruption of adhesion plaques, leading to sarcoma cell migration on laminin-111.