Produção Nacional
Glypican-3 induces a mesenchymal to epithelial transition in human breast cancer cells
2016; Impact Journals LLC; Volume: 7; Issue: 37 Linguagem: Inglês
10.18632/oncotarget.11107
ISSN1949-2553
AutoresLilian F. Castillo, Rocío Tascón, María Amparo Lago Huvelle, Gisela V. Novack, María Candelaria Llorens, Ancély Ferreira dos Santos, Jorge Eduardo Shortrede, Ana M. Cabanillas, Elisa Bal de Kier Joffé, Letícia Labriola, María Giselle Peters,
Tópico(s)Wnt/β-catenin signaling in development and cancer
Resumo// Lilian Fedra Castillo 1, * , Rocío Tascón 1 , María Amparo Lago Huvelle 2, * , Gisela Novack 1 , María Candelaria Llorens 3, * , Ancely Ferreira dos Santos 4 , Jorge Shortrede 1 , Ana María Cabanillas 3, * , Elisa Bal de Kier Joffé 1, * , Leticia Labriola 4 , María Giselle Peters 1, * 1 Universidad de Buenos Aires, Instituto de Oncología “Ángel H. Roffo”, Area Investigación, Buenos Aires, Argentina 2 Universidad de Buenos Aires, CONICET, Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales (IQUIBICEN), Facultad de Ciencias Exactas y Naturales, Buenos Aires, Argentina 3 Departamento de Bioquímica Clínica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba and Centro de Investigaciones en Bioquímica Clínica e Inmunología (CIBICI-CONICET), Córdoba, Argentina 4 Biochemistry Department, Chemistry Institute, University of São Paulo, São Paulo, Brazil * Member of the National Council of Scientific and Technical Research (CONICET) Correspondence to: María Giselle Peters, email: mpeters@fmed.uba.ar , mgpeters@hotmail.com Keywords: breast cancer, glypican-3, epithelial-mesenchymal transition, invasion, metastasis Received: September 18, 2015 Accepted: July 16, 2016 Published: August 06, 2016 ABSTRACT Breast cancer is the disease with the highest impact on global health, being metastasis the main cause of death. To metastasize, carcinoma cells must reactivate a latent program called epithelial-mesenchymal transition (EMT), through which epithelial cancer cells acquire mesenchymal-like traits. Glypican-3 (GPC3), a proteoglycan involved in the regulation of proliferation and survival, has been associated with cancer. In this study we observed that the expression of GPC3 is opposite to the invasive/metastatic ability of Hs578T, MDA-MB231, ZR-75-1 and MCF-7 human breast cancer cell lines. GPC3 silencing activated growth, cell death resistance, migration, and invasive/metastatic capacity of MCF-7 cancer cells, while GPC3 overexpression inhibited these properties in MDA-MB231 tumor cell line. Moreover, silencing of GPC3 deepened the MCF-7 breast cancer cells mesenchymal characteristics, decreasing the expression of the epithelial marker E-Cadherin. On the other side, GPC3 overexpression induced the mesenchymal-epithelial transition (MET) of MDA-MB231 breast cancer cells, which re-expressed E-Cadherin and reduced the expression of vimentin and N-Cadherin. While GPC3 inhibited the canonical Wnt/β-Catenin pathway in the breast cancer cells, this inhibition did not have effect on E-Cadherin expression. We demonstrated that the transcriptional repressor of E-Cadherin - ZEB1 - is upregulated in GPC3 silenced MCF-7 cells, while it is downregulated when GPC3 was overexpressed in MDA-MB231 cells. We presented experimental evidences showing that GPC3 induces the E-Cadherin re-expression in MDA-MB231 cells through the downregulation of ZEB1. Our data indicate that GPC3 is an important regulator of EMT in breast cancer, and a potential target for procedures against breast cancer metastasis.
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