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
- Institución
- Universidad Nacional de La Plata
- OAI Identificador
- oai:sedici.unlp.edu.ar:10915/107851
Ver los metadatos del registro completo
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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:UNLP2025-09-29T11:23:52Zoai: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:13292025-09-29 11:23:52.821SEDICI (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 |
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http://sedici.unlp.edu.ar/handle/10915/107851 |
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