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High expression of apoptosis protein (Api-5) in chemoresistant triple-negative breast cancers: an innovative target

Anti-apoptotic protein-5 (API-5) is a survival protein interacting with the protein acinus, preventing its cleavage by caspase-3 and thus inhibiting apoptosis. We studied the effect of targeting API-5 in chemoresistant triple negative breast cancers (TNBCs), to reverse chemoresistance. 78 TNBC biops...

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Autores principales: Bousquet, Guilhem, Feugeas, Jean-Paul, Gu, Yuchen, Leboeuf, Christophe, Bouchtaoui, Morad El, Lu, He, Espié, Marc, Janin, Anne, Benedetto, Melanie Di
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6859922/
https://www.ncbi.nlm.nih.gov/pubmed/31762939
http://dx.doi.org/10.18632/oncotarget.27312
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author Bousquet, Guilhem
Feugeas, Jean-Paul
Gu, Yuchen
Leboeuf, Christophe
Bouchtaoui, Morad El
Lu, He
Espié, Marc
Janin, Anne
Benedetto, Melanie Di
author_facet Bousquet, Guilhem
Feugeas, Jean-Paul
Gu, Yuchen
Leboeuf, Christophe
Bouchtaoui, Morad El
Lu, He
Espié, Marc
Janin, Anne
Benedetto, Melanie Di
author_sort Bousquet, Guilhem
collection PubMed
description Anti-apoptotic protein-5 (API-5) is a survival protein interacting with the protein acinus, preventing its cleavage by caspase-3 and thus inhibiting apoptosis. We studied the effect of targeting API-5 in chemoresistant triple negative breast cancers (TNBCs), to reverse chemoresistance. 78 TNBC biopsies from patients with different responses to chemotherapy were analysed for API-5 expression before any treatment. Further studies on API-5 expression and inhibition were performed on patient-derived TNBC xenografts, one highly sensitive to chemotherapies (XBC-S) and the other resistant to most tested drugs (XBC-R). In situ assessments of necrosis, cell proliferation, angiogenesis, and apoptosis in response to anti-API-5 peptide were performed on the TNBC xenografts. Clinical analyses of the 78 TNBC biopsies revealed that API-5 was more markedly expressed in endothelial cells before any treatment among patients with chemoresistant TNBC, and this was associated with greater micro-vessel density. A transcriptomic analysis of xenografted tumors showed an involvement of anti-apoptotic genes in the XBC-R model, and API-5 expression was higher in XBC-R endothelial cells. API-5 expression was also correlated with hypoxic stress conditions both in vitro and in vivo. 28 days of anti-API-5 peptide efficiently inhibited the XBC-R xenograft via caspase-3 apoptosis. This inhibition was associated with major inhibition of angiogenesis associated with necrosis and apoptosis. API-5 protein could be a valid therapeutic target in chemoresistant metastatic TNBC.
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spelling pubmed-68599222019-11-22 High expression of apoptosis protein (Api-5) in chemoresistant triple-negative breast cancers: an innovative target Bousquet, Guilhem Feugeas, Jean-Paul Gu, Yuchen Leboeuf, Christophe Bouchtaoui, Morad El Lu, He Espié, Marc Janin, Anne Benedetto, Melanie Di Oncotarget Research Paper Anti-apoptotic protein-5 (API-5) is a survival protein interacting with the protein acinus, preventing its cleavage by caspase-3 and thus inhibiting apoptosis. We studied the effect of targeting API-5 in chemoresistant triple negative breast cancers (TNBCs), to reverse chemoresistance. 78 TNBC biopsies from patients with different responses to chemotherapy were analysed for API-5 expression before any treatment. Further studies on API-5 expression and inhibition were performed on patient-derived TNBC xenografts, one highly sensitive to chemotherapies (XBC-S) and the other resistant to most tested drugs (XBC-R). In situ assessments of necrosis, cell proliferation, angiogenesis, and apoptosis in response to anti-API-5 peptide were performed on the TNBC xenografts. Clinical analyses of the 78 TNBC biopsies revealed that API-5 was more markedly expressed in endothelial cells before any treatment among patients with chemoresistant TNBC, and this was associated with greater micro-vessel density. A transcriptomic analysis of xenografted tumors showed an involvement of anti-apoptotic genes in the XBC-R model, and API-5 expression was higher in XBC-R endothelial cells. API-5 expression was also correlated with hypoxic stress conditions both in vitro and in vivo. 28 days of anti-API-5 peptide efficiently inhibited the XBC-R xenograft via caspase-3 apoptosis. This inhibition was associated with major inhibition of angiogenesis associated with necrosis and apoptosis. API-5 protein could be a valid therapeutic target in chemoresistant metastatic TNBC. Impact Journals LLC 2019-11-12 /pmc/articles/PMC6859922/ /pubmed/31762939 http://dx.doi.org/10.18632/oncotarget.27312 Text en http://creativecommons.org/licenses/by/3.0/ Copyright: Bousquet et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License 3.0 (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Bousquet, Guilhem
Feugeas, Jean-Paul
Gu, Yuchen
Leboeuf, Christophe
Bouchtaoui, Morad El
Lu, He
Espié, Marc
Janin, Anne
Benedetto, Melanie Di
High expression of apoptosis protein (Api-5) in chemoresistant triple-negative breast cancers: an innovative target
title High expression of apoptosis protein (Api-5) in chemoresistant triple-negative breast cancers: an innovative target
title_full High expression of apoptosis protein (Api-5) in chemoresistant triple-negative breast cancers: an innovative target
title_fullStr High expression of apoptosis protein (Api-5) in chemoresistant triple-negative breast cancers: an innovative target
title_full_unstemmed High expression of apoptosis protein (Api-5) in chemoresistant triple-negative breast cancers: an innovative target
title_short High expression of apoptosis protein (Api-5) in chemoresistant triple-negative breast cancers: an innovative target
title_sort high expression of apoptosis protein (api-5) in chemoresistant triple-negative breast cancers: an innovative target
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6859922/
https://www.ncbi.nlm.nih.gov/pubmed/31762939
http://dx.doi.org/10.18632/oncotarget.27312
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