Glypican-3 induces a mesenchymal to epithelial transition in human breast cancer cells
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. Gly...
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todo:paper_19492553_v7_n37_p60133_Castillo2023-10-03T16:37:16Z Glypican-3 induces a mesenchymal to epithelial transition in human breast cancer cells 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. 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 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. Fil:Peters, M.G. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. JOUR info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar http://hdl.handle.net/20.500.12110/paper_19492553_v7_n37_p60133_Castillo |
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Universidad de Buenos Aires |
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I-28 |
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R-134 |
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Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| topic |
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 |
| spellingShingle |
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 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 |
| topic_facet |
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 |
| description |
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. |
| format |
JOUR |
| author |
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. |
| author_facet |
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. |
| author_sort |
Castillo, L.F. |
| title |
Glypican-3 induces a mesenchymal to epithelial transition in human breast cancer cells |
| title_short |
Glypican-3 induces a mesenchymal to epithelial transition in human breast cancer cells |
| title_full |
Glypican-3 induces a mesenchymal to epithelial transition in human breast cancer cells |
| title_fullStr |
Glypican-3 induces a mesenchymal to epithelial transition in human breast cancer cells |
| title_full_unstemmed |
Glypican-3 induces a mesenchymal to epithelial transition in human breast cancer cells |
| title_sort |
glypican-3 induces a mesenchymal to epithelial transition in human breast cancer cells |
| url |
http://hdl.handle.net/20.500.12110/paper_19492553_v7_n37_p60133_Castillo |
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