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





The cover for issue 61 of Oncotarget features Figure 4, “The influence of stress conditions on API-5 expression and inhibition,” by Bousquet, et al.


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

and the other resistant to most tested drugs.

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.


Dr. Melanie Di Benedetto

and Dr. Guilhem Bousquet said, ”

Apoptosis Inhibitor-5 (API-5) also called Anti-Apoptosis Clone 11 (AAC-11) is a 58-kDa nuclear protein highly conserved across species.

API-5 was originally identified as an

anti-apoptotic protein

in mouse fibroblasts and in human cervical carcinoma cell lines, in which API-5 significantly enhanced cell survival after serum deprivation or ultraviolet sensitization.

In vitro, a decrease in API-5 expression sensitized human cancer cell lines to apoptosis, and increased their sensitivity to anticancer drugs.

In human

osteocarcinoma

cells, API-5 promotes survival through the inhibition of an E2 promoter-binding factor, and the integrity of the leucine zipper domain is required for the anti-apoptotic functions of API-5.

Previous authors engineered an anti-API5 peptide composed of the LZ domain fused with the Antennapedia/Penetrating protein domain since the integrity of this domain is essential for the function of API-5. This LZ peptide is able to penetrate cells in vitro, and to cancel the API-5/acinus interaction.

In this pre-clinical study, the authors studied the expression of API-5 in patients with chemotherapy-resistant

TNBC

and the inhibition of API-5 in a resistant TNBC xenograft model.

The Benedetto/Bousquet Research Team concluded that Hypoxia is associated with drug resistance and they have previously demonstrated a link between

cancer stem-cells

, hypoxic niches and resistance to sunitinib in renal cell carcinoma.

In vivo,

hypoxia

has been shown to induce resistance to apoptosis in human cervical cancer cell lines through a selection of p53-mutated cells.


Full text



https:/

/

doi.

org/

10.

18632/

oncotarget.

27312


Correspondence to

– Melanie Di Benedetto –

[email protected]

and Guilhem Bousquet –

[email protected]


Keywords




triple-negative breast cancer

,

chemotherapy resistance

,

apoptosis-inhibitor-5

,

peptide

,

anti-angiogenic therapy

This part of information is sourced from https://www.eurekalert.org/pub_releases/2019-11/ijl-heo111319.php

@RYANJAMESJESSUP
800-922-0957 x105
[email protected]
http://www.impactjournals.com 

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