CIBICI   14215
CENTRO DE INVESTIGACION EN BIOQUIMICA CLINICA E INMUNOLOGIA
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Glypican-3 (GPC3) Induces a Mesenchymal-Epithelial Transition in Human Breast Cancer Cells Lines
Autor/es:
CASTILLO, L; NOVACK, G; BAL DE KIER JOFFE, E; HUVELLE, M; CABANILLAS, ANA MARIA; TASCON, R; LLORENS, MC; PETERS, MG
Lugar:
Buenos Aires
Reunión:
Congreso; Simposio Internacional Programa RAICES Red de Científicos Argentinos en el Noreste de EE.UU. ?Ganando la guerra contra el cáncer?; 2016
Institución organizadora:
Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires
Resumen:
Glypicans constitute a family of heparan sulphate proteoglycans. Since GPC3has been linked to cancer, herein we generated a human breast cancer cellmodel to evaluate the role of GPC3 in tumor progression. GPC3 expression wasblocked in MCF-7 cells (poorly-metastatic, GPC3 +) by siRNA (generating MCF-7-shGPC3 sublines), and overexpressed in MDA-MB231cells (metastatic, GPC3-) by viral infection (producing MDA-MB231-GPC3 sublines).We performed in vitro and in vivo characterization of this model. GPC3 silencedMCF-7 cells acquired F-actin stress fibers, enhanced their clonogenic ability(Colony number 130 ?shGPC3 vs. 37 ?sh Negative Control (NC)) as well as theirmigration (Wound coverage (%): 15 -shGPC3 vs. 2 -shNC), were lesssusceptible to cell death (Cell death (%): 21.6 -shGPC3 vs. 34 -shNC),diminished the expression of E-Cadherin while acquired the mesenchymalmarker N-Cadherin, and were more invasive and metastatic in vivo. These cellsexhibited an upregulation of the EMT-transcription factor ZEB1, and thecanonical Wnt/β-Catenin signaling pathway was activated.GPC3 overexpressing MDA-MB231 cells misplaced their fibroblast-likeappearance as well as their F-actin stress fibers, repressed their clonogenicity(Colony number: 8 -GPC3 vs. 40 -vector) and migratory capacity (Woundcoverage (%): 10 -GPC3 vs. 90 -vector), were more sensitive to death in starvingcondition (Cell death (%) 30 -GPC3 vs. 6.5 -vector), got the ability to form ECadherindependent-spheroids, reexpressed E-Cadherin and downregulated themesenchymal markers N-Cadherin and Vimentin, while were less invasive andmetastatic in vivo. The expression of ZEB1 was diminished, as well as theactivity of the canonical Wnt/β-Catenin signaling pathway. However, whencanonical Wnt signaling was activated by LiCl, the expression of E-Cadherin didnot change.Our results show that GPC3 induces MET in breast cancer cells by regulatingZEB1 expression. The MET induced by GPC3 would be independent from thecanonical Wnt/ β-Catenin signaling pathway.