CDC42 as an epigenetic regulator of ID4 in breast cancer

Autores
Nasif, Daniela Lucía; Laurito, Sergio Roberto; Roque Moreno, Maria; Branham, Maria Teresita
Año de publicación
2019
Idioma
inglés
Tipo de recurso
documento de conferencia
Estado
versión publicada
Descripción
CDC42 as an epigenetic regulator of ID4 in breast cancerDaniela Nasif, Sergio Laurito, María Roqué and María T. BranhamIHEM, National University of Cuyo, CONICET, Mendoza, Argentina.Introduction: Breast cancer can be classified as luminal A, luminal B, human epidermal growth factor receptor 2 and triple-negative (TN). Clinically, TN subtype has an aggressive nature, higher rates of relapse and shorter overall survival. Inhibitor of differentiation proteins 1, 2, 3 and 4 (ID1?4), are dominant negative regulators of the basic helix-loop helix family of transcription factors. In TN tumors, increased expression of ID4 proteins has been associated with reversion to an embryonic-like state, high rates of proliferation and migration. We have shown that ID4 promoter hypomethylation is associated with TN subtype. Also, that ID4 hypomethylation is associated with BRCAness phenotype and BRCA1 downregulation. Cdc42 is a plasma membrane-associated small GTPase, whose expression is dysregulated in several tumor types. Here we show that the overexpression of CDC42 reduced the aggressive phenotype of the MDA-MB-231 cells through the methylation of ID4 promoter and upregulation of BRCA1. Methods and Results: MDA-MB321 cell lines were transfected with a CDC42-GFP vector. ID4 methylation was measured by droplet digital, MS PCR and MS-MLPA assay. ID4 methylation increased after CDC42 transfection (p<0.05). WB assay revealed that ID4 protein expression decreased significantly after CDC42 transfection and BRCA1 protein expression increased in the CDC42 transfected cells (p<0.05). Given that ID4 increased expression is associated with stem cell phenotype, we evaluated the expression of the breast cancer stem cell marker EPCAM in CDC42 transfected cells. WB assay revealed that EPCAM expression decreased in CDC42 treated cells. To understand CDC42-driven transcriptional regulation we used RNAseq data from TCGA. Unsupervised hierarchical clustering analysis revealed that CDC42 expression clusters with: MBD2, CASP7, STAT1, BMT1, YY1, CTNNB1, ZBTB33, STAT3 and BRCA1. Enrichment Analysis identified the GO terms: repressing of transcription binding and methyl CpG binding (p<0.0001). Conclusion CDC42 activates an epigenetic signaling pathway that induces ID4 methylation in MDA-MB231 cell lines.
Fil: Nasif, Daniela Lucía. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; Argentina
Fil: Laurito, Sergio Roberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; Argentina
Fil: Roque Moreno, Maria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; Argentina
Fil: Branham, Maria Teresita. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; Argentina
48th Annual Meeting of the Brazilian Society for Biochemistry and Molecular Biology
Aguas de Lindoia
Brasil
Sociedade Brasileira de Bioquímica e Biologia Molecular
Materia
CDC42
ID4
EPIGENETIC
BREAST CANCER
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/215765
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/215765
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling CDC42 as an epigenetic regulator of ID4 in breast cancerNasif, Daniela LucíaLaurito, Sergio RobertoRoque Moreno, MariaBranham, Maria TeresitaCDC42ID4EPIGENETICBREAST CANCERhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1CDC42 as an epigenetic regulator of ID4 in breast cancerDaniela Nasif, Sergio Laurito, María Roqué and María T. BranhamIHEM, National University of Cuyo, CONICET, Mendoza, Argentina.Introduction: Breast cancer can be classified as luminal A, luminal B, human epidermal growth factor receptor 2 and triple-negative (TN). Clinically, TN subtype has an aggressive nature, higher rates of relapse and shorter overall survival. Inhibitor of differentiation proteins 1, 2, 3 and 4 (ID1?4), are dominant negative regulators of the basic helix-loop helix family of transcription factors. In TN tumors, increased expression of ID4 proteins has been associated with reversion to an embryonic-like state, high rates of proliferation and migration. We have shown that ID4 promoter hypomethylation is associated with TN subtype. Also, that ID4 hypomethylation is associated with BRCAness phenotype and BRCA1 downregulation. Cdc42 is a plasma membrane-associated small GTPase, whose expression is dysregulated in several tumor types. Here we show that the overexpression of CDC42 reduced the aggressive phenotype of the MDA-MB-231 cells through the methylation of ID4 promoter and upregulation of BRCA1. Methods and Results: MDA-MB321 cell lines were transfected with a CDC42-GFP vector. ID4 methylation was measured by droplet digital, MS PCR and MS-MLPA assay. ID4 methylation increased after CDC42 transfection (p<0.05). WB assay revealed that ID4 protein expression decreased significantly after CDC42 transfection and BRCA1 protein expression increased in the CDC42 transfected cells (p<0.05). Given that ID4 increased expression is associated with stem cell phenotype, we evaluated the expression of the breast cancer stem cell marker EPCAM in CDC42 transfected cells. WB assay revealed that EPCAM expression decreased in CDC42 treated cells. To understand CDC42-driven transcriptional regulation we used RNAseq data from TCGA. Unsupervised hierarchical clustering analysis revealed that CDC42 expression clusters with: MBD2, CASP7, STAT1, BMT1, YY1, CTNNB1, ZBTB33, STAT3 and BRCA1. Enrichment Analysis identified the GO terms: repressing of transcription binding and methyl CpG binding (p<0.0001). Conclusion CDC42 activates an epigenetic signaling pathway that induces ID4 methylation in MDA-MB231 cell lines.Fil: Nasif, Daniela Lucía. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; ArgentinaFil: Laurito, Sergio Roberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; ArgentinaFil: Roque Moreno, Maria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; ArgentinaFil: Branham, Maria Teresita. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; Argentina48th Annual Meeting of the Brazilian Society for Biochemistry and Molecular BiologyAguas de LindoiaBrasilSociedade Brasileira de Bioquímica e Biologia MolecularSociedade Brasileira de Bioquímica e Biologia MolecularGomes de Silva, Jeferson2019info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/conferenceObjectReuniónBookhttp://purl.org/coar/resource_type/c_5794info:ar-repo/semantics/documentoDeConferenciaapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/215765CDC42 as an epigenetic regulator of ID4 in breast cancer; 48th Annual Meeting of the Brazilian Society for Biochemistry and Molecular Biology; Aguas de Lindoia; Brasil; 2019; 28-28CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www2.sbbq.org.br/reuniao/images/Livro_Resumos_2019.pdfInternacionalinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T10:03:20Zoai:ri.conicet.gov.ar:11336/215765instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-03 10:03:20.921CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv CDC42 as an epigenetic regulator of ID4 in breast cancer
title CDC42 as an epigenetic regulator of ID4 in breast cancer
spellingShingle CDC42 as an epigenetic regulator of ID4 in breast cancer
Nasif, Daniela Lucía
CDC42
ID4
EPIGENETIC
BREAST CANCER
title_short CDC42 as an epigenetic regulator of ID4 in breast cancer
title_full CDC42 as an epigenetic regulator of ID4 in breast cancer
title_fullStr CDC42 as an epigenetic regulator of ID4 in breast cancer
title_full_unstemmed CDC42 as an epigenetic regulator of ID4 in breast cancer
title_sort CDC42 as an epigenetic regulator of ID4 in breast cancer
dc.creator.none.fl_str_mv Nasif, Daniela Lucía
Laurito, Sergio Roberto
Roque Moreno, Maria
Branham, Maria Teresita
author Nasif, Daniela Lucía
author_facet Nasif, Daniela Lucía
Laurito, Sergio Roberto
Roque Moreno, Maria
Branham, Maria Teresita
author_role author
author2 Laurito, Sergio Roberto
Roque Moreno, Maria
Branham, Maria Teresita
author2_role author
author
author
dc.contributor.none.fl_str_mv Gomes de Silva, Jeferson
dc.subject.none.fl_str_mv CDC42
ID4
EPIGENETIC
BREAST CANCER
topic CDC42
ID4
EPIGENETIC
BREAST CANCER
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv CDC42 as an epigenetic regulator of ID4 in breast cancerDaniela Nasif, Sergio Laurito, María Roqué and María T. BranhamIHEM, National University of Cuyo, CONICET, Mendoza, Argentina.Introduction: Breast cancer can be classified as luminal A, luminal B, human epidermal growth factor receptor 2 and triple-negative (TN). Clinically, TN subtype has an aggressive nature, higher rates of relapse and shorter overall survival. Inhibitor of differentiation proteins 1, 2, 3 and 4 (ID1?4), are dominant negative regulators of the basic helix-loop helix family of transcription factors. In TN tumors, increased expression of ID4 proteins has been associated with reversion to an embryonic-like state, high rates of proliferation and migration. We have shown that ID4 promoter hypomethylation is associated with TN subtype. Also, that ID4 hypomethylation is associated with BRCAness phenotype and BRCA1 downregulation. Cdc42 is a plasma membrane-associated small GTPase, whose expression is dysregulated in several tumor types. Here we show that the overexpression of CDC42 reduced the aggressive phenotype of the MDA-MB-231 cells through the methylation of ID4 promoter and upregulation of BRCA1. Methods and Results: MDA-MB321 cell lines were transfected with a CDC42-GFP vector. ID4 methylation was measured by droplet digital, MS PCR and MS-MLPA assay. ID4 methylation increased after CDC42 transfection (p<0.05). WB assay revealed that ID4 protein expression decreased significantly after CDC42 transfection and BRCA1 protein expression increased in the CDC42 transfected cells (p<0.05). Given that ID4 increased expression is associated with stem cell phenotype, we evaluated the expression of the breast cancer stem cell marker EPCAM in CDC42 transfected cells. WB assay revealed that EPCAM expression decreased in CDC42 treated cells. To understand CDC42-driven transcriptional regulation we used RNAseq data from TCGA. Unsupervised hierarchical clustering analysis revealed that CDC42 expression clusters with: MBD2, CASP7, STAT1, BMT1, YY1, CTNNB1, ZBTB33, STAT3 and BRCA1. Enrichment Analysis identified the GO terms: repressing of transcription binding and methyl CpG binding (p<0.0001). Conclusion CDC42 activates an epigenetic signaling pathway that induces ID4 methylation in MDA-MB231 cell lines.
Fil: Nasif, Daniela Lucía. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; Argentina
Fil: Laurito, Sergio Roberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; Argentina
Fil: Roque Moreno, Maria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; Argentina
Fil: Branham, Maria Teresita. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; Argentina
48th Annual Meeting of the Brazilian Society for Biochemistry and Molecular Biology
Aguas de Lindoia
Brasil
Sociedade Brasileira de Bioquímica e Biologia Molecular
description CDC42 as an epigenetic regulator of ID4 in breast cancerDaniela Nasif, Sergio Laurito, María Roqué and María T. BranhamIHEM, National University of Cuyo, CONICET, Mendoza, Argentina.Introduction: Breast cancer can be classified as luminal A, luminal B, human epidermal growth factor receptor 2 and triple-negative (TN). Clinically, TN subtype has an aggressive nature, higher rates of relapse and shorter overall survival. Inhibitor of differentiation proteins 1, 2, 3 and 4 (ID1?4), are dominant negative regulators of the basic helix-loop helix family of transcription factors. In TN tumors, increased expression of ID4 proteins has been associated with reversion to an embryonic-like state, high rates of proliferation and migration. We have shown that ID4 promoter hypomethylation is associated with TN subtype. Also, that ID4 hypomethylation is associated with BRCAness phenotype and BRCA1 downregulation. Cdc42 is a plasma membrane-associated small GTPase, whose expression is dysregulated in several tumor types. Here we show that the overexpression of CDC42 reduced the aggressive phenotype of the MDA-MB-231 cells through the methylation of ID4 promoter and upregulation of BRCA1. Methods and Results: MDA-MB321 cell lines were transfected with a CDC42-GFP vector. ID4 methylation was measured by droplet digital, MS PCR and MS-MLPA assay. ID4 methylation increased after CDC42 transfection (p<0.05). WB assay revealed that ID4 protein expression decreased significantly after CDC42 transfection and BRCA1 protein expression increased in the CDC42 transfected cells (p<0.05). Given that ID4 increased expression is associated with stem cell phenotype, we evaluated the expression of the breast cancer stem cell marker EPCAM in CDC42 transfected cells. WB assay revealed that EPCAM expression decreased in CDC42 treated cells. To understand CDC42-driven transcriptional regulation we used RNAseq data from TCGA. Unsupervised hierarchical clustering analysis revealed that CDC42 expression clusters with: MBD2, CASP7, STAT1, BMT1, YY1, CTNNB1, ZBTB33, STAT3 and BRCA1. Enrichment Analysis identified the GO terms: repressing of transcription binding and methyl CpG binding (p<0.0001). Conclusion CDC42 activates an epigenetic signaling pathway that induces ID4 methylation in MDA-MB231 cell lines.
publishDate 2019
dc.date.none.fl_str_mv 2019
dc.type.none.fl_str_mv info:eu-repo/semantics/publishedVersion
info:eu-repo/semantics/conferenceObject
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http://purl.org/coar/resource_type/c_5794
info:ar-repo/semantics/documentoDeConferencia
status_str publishedVersion
format conferenceObject
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/215765
CDC42 as an epigenetic regulator of ID4 in breast cancer; 48th Annual Meeting of the Brazilian Society for Biochemistry and Molecular Biology; Aguas de Lindoia; Brasil; 2019; 28-28
CONICET Digital
CONICET
url http://hdl.handle.net/11336/215765
identifier_str_mv CDC42 as an epigenetic regulator of ID4 in breast cancer; 48th Annual Meeting of the Brazilian Society for Biochemistry and Molecular Biology; Aguas de Lindoia; Brasil; 2019; 28-28
CONICET Digital
CONICET
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language eng
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dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
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application/pdf
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dc.coverage.none.fl_str_mv Internacional
dc.publisher.none.fl_str_mv Sociedade Brasileira de Bioquímica e Biologia Molecular
publisher.none.fl_str_mv Sociedade Brasileira de Bioquímica e Biologia Molecular
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
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