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.
Departamento de Radiologia e Oncologia, Faculdade de Medicina da Universidade de São Paulo, São Paulo, São Paulo, Brazil.
Fabiana H M
FH
Melo
Diego
D
Butera
Mara de Souza
Mde S
Junqueira
Daniel K
DK
Hsu
Ana Maria Moura
AM
da Silva
Fu-Tong
FT
Liu
Marinilice F
MF
Santos
Roger
R
Chammas
D000818:Animals; D004789:Enzyme Activation; D037502:Galectin 3 / Q000235:genetics / Q000502:physiology*; D051379:Mice; D041681:NIH 3T3 Cells; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D015398:Signal Transduction; D014407:Tumor Cells, Cultured
D037502:Galectin 3; D019869:Phosphatidylinositol 3-Kinases