Artículo

Castillo, L.F.; Tascón, R.; Huvelle, M.A.L.; Novack, G.; Llorens, M.C.; Santos, A.F.; Shortrede, J.; Cabanillas, A.M.; Joffé, E.B.K.; Labriola, L.; Peters, M.G. "Glypican-3 induces a mesenchymal to epithelial transition in human breast cancer cells" (2016) Oncotarget. 7(37):60133-60154
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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.

Registro:

Documento: Artículo
Título:Glypican-3 induces a mesenchymal to epithelial transition in human breast cancer cells
Autor:Castillo, L.F.; Tascón, R.; Huvelle, M.A.L.; Novack, G.; Llorens, M.C.; Santos, A.F.; Shortrede, J.; Cabanillas, A.M.; Joffé, E.B.K.; Labriola, L.; Peters, M.G.
Filiación:Universidad de Buenos Aires, Instituto de Oncología 'ángel H. Roffo', Area Investigación, Buenos Aires, Argentina
Universidad de Buenos Aires, CONICET, Instituto de Química Biológica, Facultad de Ciencias Exactas y Naturales (IQUIBICEN), Facultad de Ciencias Exactas y Naturales, Buenos Aires, Argentina
Departamento de Bioquímica Clínica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Centro de Investigaciones en Bioquímica Clínica e Inmunología (CIBICI-CONICET), Córdoba, Argentina
Biochemistry Department, Chemistry Institute, University of São Paulo, São Paulo, Brazil
Palabras clave:Breast cancer; Epithelial-mesenchymal transition; Glypican-3; Invasion; Metastasis; beta catenin; glypican 3; nerve cell adhesion molecule; uvomorulin; Wnt protein; cadherin; glypican; GPC3 protein, human; transcription factor ZEB1; ZEB1 protein, human; animal experiment; animal model; animal tissue; apoptosis; Article; breast cancer; breast cancer cell line; cancer cell; cell death; cell growth; cell invasion; cell migration; cell structure; cell viability; controlled study; down regulation; epithelial mesenchymal transition; female; histopathology; human; human cell; immunofluorescence; immunohistochemistry; in vitro study; in vivo study; MCF 7 cell line; MDA MB231 cell line; metastasis potential; mouse; nonhuman; protein expression; real time polymerase chain reaction; tumor xenograft; upregulation; Western blotting; ZR 75 1 cell line; animal; breast tumor; cell motion; cell proliferation; epithelial mesenchymal transition; gene expression regulation; genetics; MCF-7 cell line; metabolism; nude mouse; pathology; RNA interference; tumor cell line; tumor volume; xenograft; Animals; Breast Neoplasms; Cadherins; Cell Line, Tumor; Cell Movement; Cell Proliferation; Epithelial-Mesenchymal Transition; Female; Gene Expression Regulation, Neoplastic; Glypicans; Humans; MCF-7 Cells; Mice, Nude; RNA Interference; Transplantation, Heterologous; Tumor Burden; Zinc Finger E-box-Binding Homeobox 1
Año:2016
Volumen:7
Número:37
Página de inicio:60133
Página de fin:60154
DOI: http://dx.doi.org/10.18632/oncotarget.11107
Título revista:Oncotarget
Título revista abreviado:Oncotarget
ISSN:19492553
CAS:uvomorulin, 112956-45-3; Cadherins; Glypicans; GPC3 protein, human; ZEB1 protein, human; Zinc Finger E-box-Binding Homeobox 1
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_19492553_v7_n37_p60133_Castillo

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Citas:

---------- APA ----------
Castillo, L.F., Tascón, R., Huvelle, M.A.L., Novack, G., Llorens, M.C., Santos, A.F., Shortrede, J.,..., Peters, M.G. (2016) . Glypican-3 induces a mesenchymal to epithelial transition in human breast cancer cells. Oncotarget, 7(37), 60133-60154.
http://dx.doi.org/10.18632/oncotarget.11107
---------- CHICAGO ----------
Castillo, L.F., Tascón, R., Huvelle, M.A.L., Novack, G., Llorens, M.C., Santos, A.F., et al. "Glypican-3 induces a mesenchymal to epithelial transition in human breast cancer cells" . Oncotarget 7, no. 37 (2016) : 60133-60154.
http://dx.doi.org/10.18632/oncotarget.11107
---------- MLA ----------
Castillo, L.F., Tascón, R., Huvelle, M.A.L., Novack, G., Llorens, M.C., Santos, A.F., et al. "Glypican-3 induces a mesenchymal to epithelial transition in human breast cancer cells" . Oncotarget, vol. 7, no. 37, 2016, pp. 60133-60154.
http://dx.doi.org/10.18632/oncotarget.11107
---------- VANCOUVER ----------
Castillo, L.F., Tascón, R., Huvelle, M.A.L., Novack, G., Llorens, M.C., Santos, A.F., et al. Glypican-3 induces a mesenchymal to epithelial transition in human breast cancer cells. Oncotarget. 2016;7(37):60133-60154.
http://dx.doi.org/10.18632/oncotarget.11107