Humanin Promotes Tumor Progression in Experimental Triple Negative Breast Cancer

Autores
Moreno Ayala, Mariela A.; Gottardo, María Florencia; Zuccato, Camila Florencia; Pidre, Matías Luis; Nicola Candia, Alejandro Javier; Asad, Antonela Sofia; Imsen, Mercedes; Romanowski, Víctor; Cretón, Aldo; Isla Larrain, Marina Teresita; Seilicovich, Adriana; Candolfi, Marianela
Año de publicación
2020
Idioma
español castellano
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Humanin (HN) is a mitochondrial-derived peptide with cytoprotective efect in many tissues. Administration of HN analogs has been proposed as therapeutic approach for degenerative diseases. Although HN has been shown to protect normal tissues from chemotherapy, its role in tumor pathogenesis is poorly understood. Here, we evaluated the efect of HN on the progression of experimental triple negative breast cancer (TNBC). The meta-analysis of transcriptomic data from The Cancer Genome Atlas indicated that HN and its receptors are expressed in breast cancer specimens. By immunohistochemistry we observed up-regulation of HN in TNBC biopsies when compared to mammary gland sections from healthy donors. Addition of exogenous HN protected TNBC cells from apoptotic stimuli whereas shRNA-mediated HN silencing reduced their viability and enhanced their chemo-sensitivity. Systemic administration of HN in TNBC-bearing mice reduced tumor apoptotic rate, impaired the antitumor and anti-metastatic efect of chemotherapy and stimulated tumor progression, accelerating tumor growth and development of spontaneous lung metastases. These fndings suggest that HN may exert pro-tumoral efects and thus, caution should be taken when using exogenous HN to treat degenerative diseases. In addition, our study suggests that HN blockade could constitute a therapeutic strategy to improve the efcacy of chemotherapy in breast cancer.
Instituto de Biotecnologia y Biologia Molecular
Materia
Ciencias Médicas
Ciencias Exactas
Humanin
Tumor progression
Breast cancer
Immunohistochemistry
Nivel de accesibilidad
acceso abierto
Condiciones de uso
http://creativecommons.org/licenses/by/4.0/
Repositorio
SEDICI (UNLP)
Institución
Universidad Nacional de La Plata
OAI Identificador
oai:sedici.unlp.edu.ar:10915/107851
Acceder
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network_name_str SEDICI (UNLP)
spelling Humanin Promotes Tumor Progression in Experimental Triple Negative Breast CancerMoreno Ayala, Mariela A.Gottardo, María FlorenciaZuccato, Camila FlorenciaPidre, Matías LuisNicola Candia, Alejandro JavierAsad, Antonela SofiaImsen, MercedesRomanowski, VíctorCretón, AldoIsla Larrain, Marina TeresitaSeilicovich, AdrianaCandolfi, MarianelaCiencias MédicasCiencias ExactasHumaninTumor progressionBreast cancerImmunohistochemistryHumanin (HN) is a mitochondrial-derived peptide with cytoprotective efect in many tissues. Administration of HN analogs has been proposed as therapeutic approach for degenerative diseases. Although HN has been shown to protect normal tissues from chemotherapy, its role in tumor pathogenesis is poorly understood. Here, we evaluated the efect of HN on the progression of experimental triple negative breast cancer (TNBC). The meta-analysis of transcriptomic data from The Cancer Genome Atlas indicated that HN and its receptors are expressed in breast cancer specimens. By immunohistochemistry we observed up-regulation of HN in TNBC biopsies when compared to mammary gland sections from healthy donors. Addition of exogenous HN protected TNBC cells from apoptotic stimuli whereas shRNA-mediated HN silencing reduced their viability and enhanced their chemo-sensitivity. Systemic administration of HN in TNBC-bearing mice reduced tumor apoptotic rate, impaired the antitumor and anti-metastatic efect of chemotherapy and stimulated tumor progression, accelerating tumor growth and development of spontaneous lung metastases. These fndings suggest that HN may exert pro-tumoral efects and thus, caution should be taken when using exogenous HN to treat degenerative diseases. In addition, our study suggests that HN blockade could constitute a therapeutic strategy to improve the efcacy of chemotherapy in breast cancer.Instituto de Biotecnologia y Biologia Molecular2020info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionArticulohttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfhttp://sedici.unlp.edu.ar/handle/10915/107851spainfo:eu-repo/semantics/altIdentifier/url/http://europepmc.org/backend/ptpmcrender.fcgi?accid=PMC7244539&blobtype=pdfinfo:eu-repo/semantics/altIdentifier/issn/2045-2322info:eu-repo/semantics/altIdentifier/pmid/32444831info:eu-repo/semantics/altIdentifier/doi/10.1038/s41598-020-65381-7info:eu-repo/semantics/openAccesshttp://creativecommons.org/licenses/by/4.0/Creative Commons Attribution 4.0 International (CC BY 4.0)reponame:SEDICI (UNLP)instname:Universidad Nacional de La Platainstacron:UNLP2025-10-15T11:15:46Zoai:sedici.unlp.edu.ar:10915/107851Institucionalhttp://sedici.unlp.edu.ar/Universidad públicaNo correspondehttp://sedici.unlp.edu.ar/oai/snrdalira@sedici.unlp.edu.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:13292025-10-15 11:15:46.771SEDICI (UNLP) - Universidad Nacional de La Platafalse
dc.title.none.fl_str_mv Humanin Promotes Tumor Progression in Experimental Triple Negative Breast Cancer
title Humanin Promotes Tumor Progression in Experimental Triple Negative Breast Cancer
spellingShingle Humanin Promotes Tumor Progression in Experimental Triple Negative Breast Cancer
Moreno Ayala, Mariela A.
Ciencias Médicas
Ciencias Exactas
Humanin
Tumor progression
Breast cancer
Immunohistochemistry
title_short Humanin Promotes Tumor Progression in Experimental Triple Negative Breast Cancer
title_full Humanin Promotes Tumor Progression in Experimental Triple Negative Breast Cancer
title_fullStr Humanin Promotes Tumor Progression in Experimental Triple Negative Breast Cancer
title_full_unstemmed Humanin Promotes Tumor Progression in Experimental Triple Negative Breast Cancer
title_sort Humanin Promotes Tumor Progression in Experimental Triple Negative Breast Cancer
dc.creator.none.fl_str_mv Moreno Ayala, Mariela A.
Gottardo, María Florencia
Zuccato, Camila Florencia
Pidre, Matías Luis
Nicola Candia, Alejandro Javier
Asad, Antonela Sofia
Imsen, Mercedes
Romanowski, Víctor
Cretón, Aldo
Isla Larrain, Marina Teresita
Seilicovich, Adriana
Candolfi, Marianela
author Moreno Ayala, Mariela A.
author_facet Moreno Ayala, Mariela A.
Gottardo, María Florencia
Zuccato, Camila Florencia
Pidre, Matías Luis
Nicola Candia, Alejandro Javier
Asad, Antonela Sofia
Imsen, Mercedes
Romanowski, Víctor
Cretón, Aldo
Isla Larrain, Marina Teresita
Seilicovich, Adriana
Candolfi, Marianela
author_role author
author2 Gottardo, María Florencia
Zuccato, Camila Florencia
Pidre, Matías Luis
Nicola Candia, Alejandro Javier
Asad, Antonela Sofia
Imsen, Mercedes
Romanowski, Víctor
Cretón, Aldo
Isla Larrain, Marina Teresita
Seilicovich, Adriana
Candolfi, Marianela
author2_role author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Ciencias Médicas
Ciencias Exactas
Humanin
Tumor progression
Breast cancer
Immunohistochemistry
topic Ciencias Médicas
Ciencias Exactas
Humanin
Tumor progression
Breast cancer
Immunohistochemistry
dc.description.none.fl_txt_mv Humanin (HN) is a mitochondrial-derived peptide with cytoprotective efect in many tissues. Administration of HN analogs has been proposed as therapeutic approach for degenerative diseases. Although HN has been shown to protect normal tissues from chemotherapy, its role in tumor pathogenesis is poorly understood. Here, we evaluated the efect of HN on the progression of experimental triple negative breast cancer (TNBC). The meta-analysis of transcriptomic data from The Cancer Genome Atlas indicated that HN and its receptors are expressed in breast cancer specimens. By immunohistochemistry we observed up-regulation of HN in TNBC biopsies when compared to mammary gland sections from healthy donors. Addition of exogenous HN protected TNBC cells from apoptotic stimuli whereas shRNA-mediated HN silencing reduced their viability and enhanced their chemo-sensitivity. Systemic administration of HN in TNBC-bearing mice reduced tumor apoptotic rate, impaired the antitumor and anti-metastatic efect of chemotherapy and stimulated tumor progression, accelerating tumor growth and development of spontaneous lung metastases. These fndings suggest that HN may exert pro-tumoral efects and thus, caution should be taken when using exogenous HN to treat degenerative diseases. In addition, our study suggests that HN blockade could constitute a therapeutic strategy to improve the efcacy of chemotherapy in breast cancer.
Instituto de Biotecnologia y Biologia Molecular
description Humanin (HN) is a mitochondrial-derived peptide with cytoprotective efect in many tissues. Administration of HN analogs has been proposed as therapeutic approach for degenerative diseases. Although HN has been shown to protect normal tissues from chemotherapy, its role in tumor pathogenesis is poorly understood. Here, we evaluated the efect of HN on the progression of experimental triple negative breast cancer (TNBC). The meta-analysis of transcriptomic data from The Cancer Genome Atlas indicated that HN and its receptors are expressed in breast cancer specimens. By immunohistochemistry we observed up-regulation of HN in TNBC biopsies when compared to mammary gland sections from healthy donors. Addition of exogenous HN protected TNBC cells from apoptotic stimuli whereas shRNA-mediated HN silencing reduced their viability and enhanced their chemo-sensitivity. Systemic administration of HN in TNBC-bearing mice reduced tumor apoptotic rate, impaired the antitumor and anti-metastatic efect of chemotherapy and stimulated tumor progression, accelerating tumor growth and development of spontaneous lung metastases. These fndings suggest that HN may exert pro-tumoral efects and thus, caution should be taken when using exogenous HN to treat degenerative diseases. In addition, our study suggests that HN blockade could constitute a therapeutic strategy to improve the efcacy of chemotherapy in breast cancer.
publishDate 2020
dc.date.none.fl_str_mv 2020
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
Articulo
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://sedici.unlp.edu.ar/handle/10915/107851
url http://sedici.unlp.edu.ar/handle/10915/107851
dc.language.none.fl_str_mv spa
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info:eu-repo/semantics/altIdentifier/issn/2045-2322
info:eu-repo/semantics/altIdentifier/pmid/32444831
info:eu-repo/semantics/altIdentifier/doi/10.1038/s41598-020-65381-7
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by/4.0/
Creative Commons Attribution 4.0 International (CC BY 4.0)
eu_rights_str_mv openAccess
rights_invalid_str_mv http://creativecommons.org/licenses/by/4.0/
Creative Commons Attribution 4.0 International (CC BY 4.0)
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv reponame:SEDICI (UNLP)
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reponame_str SEDICI (UNLP)
collection SEDICI (UNLP)
instname_str Universidad Nacional de La Plata
instacron_str UNLP
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repository.name.fl_str_mv SEDICI (UNLP) - Universidad Nacional de La Plata
repository.mail.fl_str_mv alira@sedici.unlp.edu.ar
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