Glypican-3 (GPC3) modulates epithelial-mesenchymal transition (EMT) of human breast cancer cells by downregulating ZEB1

LAGO HUVELLE MA; BAL DE KIER JOFFÉ E; NOVACK G; LLORENS MC; CASTILLO L; PETERS MG; CABANILLAS A

Mar del Plata

Congreso; LXI Reunión Anual de la Sociedad Argentina de Investigación Clínica,; 2016

Glypican-3 (GPC3) is a heparan sulfate proteoglycan related to cancer. Previously, we overexpressed GPC3 in MDA-MB231 human breast cancer cells (metastatic and GPC3-). We showed that GPC3 inhibits clonogenic and migratory capacities, while increases homotypic adhesion and apoptotic susceptibility. Moreover, GPC3 induced the reexpression of the epithelial marker E-Cadherin. Our results suggest that GPC3 would act as a metastatic suppressor by regulating epithelial-mesenchymal transition (EMT). In this work we observed that GPC3 overexpression induces a change in the MDA-MB231 cell morphology, from a fibroblastic to a more epithelial phenotype, as well as prevents the F-actin stress fibers formation. In vivo assays showed that GPC3 overexpression inhibits tumorigenicity (64% -vector vs 20% -GPC3; p