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 –
melanie.dibenedetto@univ-paris13.fr
and Guilhem Bousquet –
guilhem.bousquet@aphp.fr
Keywords
–
triple-negative breast cancer
,
chemotherapy resistance
,
apoptosis-inhibitor-5
,
peptide
,
anti-angiogenic therapy
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Oncotarget
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This part of information is sourced from https://www.eurekalert.org/pub_releases/2019-11/ijl-heo112219.php
Ryan James Jessup
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RYANJAMESJESSUP@IMPACTJOURNALS.COM
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