Open AccessThe antiviral drug telaprevir induces cell death by reducing FOXA1 expression in estrogen receptor α ( ERα )‐positive breast cancer cells
Author(s) -
Bartoloni Stefania,
Leone Stefano,
Pescatori Sara,
Cipolletti Manuela,
Acconcia Filippo
Publication year - 2022
Publication title -
molecular oncology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.332
H-Index - 88
eISSN - 1878-0261
pISSN - 1574-7891
DOI - 10.1002/1878-0261.13303
Subject(s) - estrogen receptor , foxa1 , cell growth , cancer research , protein kinase b , cell culture , biology , cancer cell , estrogen receptor alpha , microbiology and biotechnology , chemistry , cancer , signal transduction , breast cancer , biochemistry , genetics
Previously, we found that telaprevir (Tel), the inhibitor of hepatitis C virus NS3/4A serine protease, reduces estrogen receptor α (ERα) content at the transcriptional level without binding to the receptor, prevents ERα transcriptional activity, and inhibits basal and 17β‐estradiol (E2)‐dependent cell proliferation in different breast cancer (BC) cell lines. Here, we further characterize the Tel action mechanisms on ERα levels and function, identify a possible molecular target of Tel in BC cells, and evaluate Tel as an antiproliferative agent for BC treatment. Tel‐dependent reduction in ERα levels and function depends on a Tel‐dependent decrease in FOXA1 levels and activity. The effect of Tel is transduced by the IGF1‐R/AKT/FOXA1 pathway, with the antiviral compound interacting with IGF1‐R. Tel prevents the proliferation of several BC cell lines, while it does not affect the proliferation of normal nontransformed cell lines, and its antiproliferative effect is correlated with the ratio of FOXA1/IGF1‐R expression. In conclusion, Tel interferes with the IGF1‐R/AKT/FOXA1 pathway and induces cell death in ERα‐expressing BC cells. Thus, we propose that this antiviral could be repurposed for the treatment of ERα‐expressing BC.