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Article Dans Une Revue Oncotarget Année : 2019

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

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). 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 antiapoptotic 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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hal-03892241 , version 1 (09-12-2022)

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Guilhem Bousquet, Jean-Paul Feugeas, Yuchen Gu, Christophe Leboeuf, Morad El Bouchtaoui, et al.. High expression of apoptosis protein (Api-5) in chemoresistant triple-negative breast cancers: an innovative target. Oncotarget, 2019, 10 (61), pp.6577-6588. ⟨10.18632/oncotarget.27312⟩. ⟨hal-03892241⟩
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