The Yin and Yang of Breast Cancer: Ion Channels as Determinants of Left–Right Functional Differences

Autores
Masuelli, Sofía; Real Varela, Sebastián Martín; McMillen, Patrick; Oudin, Madeleine; Levin, Michael; Roque Moreno, Maria
Año de publicación
2023
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Breast cancer is a complex and heterogeneous disease that displays diverse molecular subtypes and clinical outcomes. Although it is known that the location of tumors can affect their biological behavior, the underlying mechanisms are not fully understood. In our previous study, we found a differential methylation profile and membrane potential between left (L)- and right (R)-sided breast tumors. In this current study, we aimed to identify the ion channels responsible for this phenomenon and determine any associated phenotypic features. To achieve this, experiments were conducted in mammary tumors in mice, human patient samples, and with data from public datasets. The results revealed that L-sided tumors have a more depolarized state than R-sided. We identified a 6-ion channel-gene signature (CACNA1C, CACNA2D2, CACNB2, KCNJ11, SCN3A, and SCN3B) associated with the side: L-tumors exhibit lower expression levels than R-tumors. Additionally, in silico analyses show that the signature correlates inversely with DNA methylation writers and with key biological processes involved in cancer progression, such as proliferation and stemness. The signature also correlates inversely with patient survival rates. In an in vivo mouse model, we confirmed that KI67 and CD44 markers were increased in L-sided tumors and a similar tendency for KI67 was found in patient L-tumors. Overall, this study provides new insights into the potential impact of anatomical location on breast cancer biology and highlights the need for further investigation into possible differential treatment options.
Fil: Masuelli, Sofía. 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: Real Varela, Sebastián Martín. 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: McMillen, Patrick. Tufts University; Estados Unidos
Fil: Oudin, Madeleine. Tufts University; Estados Unidos
Fil: Levin, Michael. Tufts University; Estados Unidos
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
Materia
BREAST CANCER
ION CHANNEL
LATERALITY
PROLIFERATION
STEMNESS
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/230508
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/230508
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling The Yin and Yang of Breast Cancer: Ion Channels as Determinants of Left–Right Functional DifferencesMasuelli, SofíaReal Varela, Sebastián MartínMcMillen, PatrickOudin, MadeleineLevin, MichaelRoque Moreno, MariaBREAST CANCERION CHANNELLATERALITYPROLIFERATIONSTEMNESShttps://purl.org/becyt/ford/3.4https://purl.org/becyt/ford/3Breast cancer is a complex and heterogeneous disease that displays diverse molecular subtypes and clinical outcomes. Although it is known that the location of tumors can affect their biological behavior, the underlying mechanisms are not fully understood. In our previous study, we found a differential methylation profile and membrane potential between left (L)- and right (R)-sided breast tumors. In this current study, we aimed to identify the ion channels responsible for this phenomenon and determine any associated phenotypic features. To achieve this, experiments were conducted in mammary tumors in mice, human patient samples, and with data from public datasets. The results revealed that L-sided tumors have a more depolarized state than R-sided. We identified a 6-ion channel-gene signature (CACNA1C, CACNA2D2, CACNB2, KCNJ11, SCN3A, and SCN3B) associated with the side: L-tumors exhibit lower expression levels than R-tumors. Additionally, in silico analyses show that the signature correlates inversely with DNA methylation writers and with key biological processes involved in cancer progression, such as proliferation and stemness. The signature also correlates inversely with patient survival rates. In an in vivo mouse model, we confirmed that KI67 and CD44 markers were increased in L-sided tumors and a similar tendency for KI67 was found in patient L-tumors. Overall, this study provides new insights into the potential impact of anatomical location on breast cancer biology and highlights the need for further investigation into possible differential treatment options.Fil: Masuelli, Sofía. 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: Real Varela, Sebastián Martín. 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: McMillen, Patrick. Tufts University; Estados UnidosFil: Oudin, Madeleine. Tufts University; Estados UnidosFil: Levin, Michael. Tufts University; Estados UnidosFil: 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; ArgentinaMolecular Diversity Preservation International2023-07info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/230508Masuelli, Sofía; Real Varela, Sebastián Martín; McMillen, Patrick; Oudin, Madeleine; Levin, Michael; et al.; The Yin and Yang of Breast Cancer: Ion Channels as Determinants of Left–Right Functional Differences; Molecular Diversity Preservation International; International Journal of Molecular Sciences; 24; 13; 7-2023; 1-191661-65961422-0067CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.mdpi.com/1422-0067/24/13/11121info:eu-repo/semantics/altIdentifier/doi/10.3390/ijms241311121info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:38:51Zoai:ri.conicet.gov.ar:11336/230508instacron: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:34982025-09-29 09:38:51.732CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv The Yin and Yang of Breast Cancer: Ion Channels as Determinants of Left–Right Functional Differences
title The Yin and Yang of Breast Cancer: Ion Channels as Determinants of Left–Right Functional Differences
spellingShingle The Yin and Yang of Breast Cancer: Ion Channels as Determinants of Left–Right Functional Differences
Masuelli, Sofía
BREAST CANCER
ION CHANNEL
LATERALITY
PROLIFERATION
STEMNESS
title_short The Yin and Yang of Breast Cancer: Ion Channels as Determinants of Left–Right Functional Differences
title_full The Yin and Yang of Breast Cancer: Ion Channels as Determinants of Left–Right Functional Differences
title_fullStr The Yin and Yang of Breast Cancer: Ion Channels as Determinants of Left–Right Functional Differences
title_full_unstemmed The Yin and Yang of Breast Cancer: Ion Channels as Determinants of Left–Right Functional Differences
title_sort The Yin and Yang of Breast Cancer: Ion Channels as Determinants of Left–Right Functional Differences
dc.creator.none.fl_str_mv Masuelli, Sofía
Real Varela, Sebastián Martín
McMillen, Patrick
Oudin, Madeleine
Levin, Michael
Roque Moreno, Maria
author Masuelli, Sofía
author_facet Masuelli, Sofía
Real Varela, Sebastián Martín
McMillen, Patrick
Oudin, Madeleine
Levin, Michael
Roque Moreno, Maria
author_role author
author2 Real Varela, Sebastián Martín
McMillen, Patrick
Oudin, Madeleine
Levin, Michael
Roque Moreno, Maria
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv BREAST CANCER
ION CHANNEL
LATERALITY
PROLIFERATION
STEMNESS
topic BREAST CANCER
ION CHANNEL
LATERALITY
PROLIFERATION
STEMNESS
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.4
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Breast cancer is a complex and heterogeneous disease that displays diverse molecular subtypes and clinical outcomes. Although it is known that the location of tumors can affect their biological behavior, the underlying mechanisms are not fully understood. In our previous study, we found a differential methylation profile and membrane potential between left (L)- and right (R)-sided breast tumors. In this current study, we aimed to identify the ion channels responsible for this phenomenon and determine any associated phenotypic features. To achieve this, experiments were conducted in mammary tumors in mice, human patient samples, and with data from public datasets. The results revealed that L-sided tumors have a more depolarized state than R-sided. We identified a 6-ion channel-gene signature (CACNA1C, CACNA2D2, CACNB2, KCNJ11, SCN3A, and SCN3B) associated with the side: L-tumors exhibit lower expression levels than R-tumors. Additionally, in silico analyses show that the signature correlates inversely with DNA methylation writers and with key biological processes involved in cancer progression, such as proliferation and stemness. The signature also correlates inversely with patient survival rates. In an in vivo mouse model, we confirmed that KI67 and CD44 markers were increased in L-sided tumors and a similar tendency for KI67 was found in patient L-tumors. Overall, this study provides new insights into the potential impact of anatomical location on breast cancer biology and highlights the need for further investigation into possible differential treatment options.
Fil: Masuelli, Sofía. 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: Real Varela, Sebastián Martín. 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: McMillen, Patrick. Tufts University; Estados Unidos
Fil: Oudin, Madeleine. Tufts University; Estados Unidos
Fil: Levin, Michael. Tufts University; Estados Unidos
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
description Breast cancer is a complex and heterogeneous disease that displays diverse molecular subtypes and clinical outcomes. Although it is known that the location of tumors can affect their biological behavior, the underlying mechanisms are not fully understood. In our previous study, we found a differential methylation profile and membrane potential between left (L)- and right (R)-sided breast tumors. In this current study, we aimed to identify the ion channels responsible for this phenomenon and determine any associated phenotypic features. To achieve this, experiments were conducted in mammary tumors in mice, human patient samples, and with data from public datasets. The results revealed that L-sided tumors have a more depolarized state than R-sided. We identified a 6-ion channel-gene signature (CACNA1C, CACNA2D2, CACNB2, KCNJ11, SCN3A, and SCN3B) associated with the side: L-tumors exhibit lower expression levels than R-tumors. Additionally, in silico analyses show that the signature correlates inversely with DNA methylation writers and with key biological processes involved in cancer progression, such as proliferation and stemness. The signature also correlates inversely with patient survival rates. In an in vivo mouse model, we confirmed that KI67 and CD44 markers were increased in L-sided tumors and a similar tendency for KI67 was found in patient L-tumors. Overall, this study provides new insights into the potential impact of anatomical location on breast cancer biology and highlights the need for further investigation into possible differential treatment options.
publishDate 2023
dc.date.none.fl_str_mv 2023-07
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/230508
Masuelli, Sofía; Real Varela, Sebastián Martín; McMillen, Patrick; Oudin, Madeleine; Levin, Michael; et al.; The Yin and Yang of Breast Cancer: Ion Channels as Determinants of Left–Right Functional Differences; Molecular Diversity Preservation International; International Journal of Molecular Sciences; 24; 13; 7-2023; 1-19
1661-6596
1422-0067
CONICET Digital
CONICET
url http://hdl.handle.net/11336/230508
identifier_str_mv Masuelli, Sofía; Real Varela, Sebastián Martín; McMillen, Patrick; Oudin, Madeleine; Levin, Michael; et al.; The Yin and Yang of Breast Cancer: Ion Channels as Determinants of Left–Right Functional Differences; Molecular Diversity Preservation International; International Journal of Molecular Sciences; 24; 13; 7-2023; 1-19
1661-6596
1422-0067
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://www.mdpi.com/1422-0067/24/13/11121
info:eu-repo/semantics/altIdentifier/doi/10.3390/ijms241311121
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Molecular Diversity Preservation International
publisher.none.fl_str_mv Molecular Diversity Preservation International
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 13.070432

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