High expression of apoptosis protein (Api-5) in chemoresistant triple-negative breast cancers: an innovative target.
Fiche publication
Date publication
novembre 2019
Journal
Oncotarget
Auteurs
Membres identifiés du Cancéropôle Est :
Pr FEUGEAS Jean-Paul
Tous les auteurs :
Bousquet G, Feugeas JP, Gu Y, Leboeuf C, Bouchtaoui ME, Lu H, Espié M, Janin A, Benedetto MD
Lien Pubmed
Résumé
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). 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 expression was higher in XBC-R endothelial cells. expression was also correlated with hypoxic stress conditions both and . 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.
Mots clés
anti-angiogenic therapy, apoptosis-inhibitor-5, chemotherapy resistance, peptide, triple-negative breast cancer
Référence
Oncotarget. 2019 Nov 12;10(61):6577-6588