By promoting cell differentiation, miR-100 sensitizes basal-like breast cancer stem cells to hormonal therapy
- Autori: Petrelli, A; Carollo, R;Cargnelutti, M;Iovino, F; Callari, M; Cimino, D; Todaro, M; Mangiapane, LR; Giammona, A; Cordova, A; Montemurro, F; Taverna, D; Daidone, MG; Stassi, G; Giordano S
- Anno di pubblicazione: 2015
- Tipologia: Articolo in rivista (Articolo in rivista)
- OA Link: http://hdl.handle.net/10447/103963
Abstract
Basal-like breast cancer is an aggressive tumor subtype with a poor response to conventional therapies. Tumor formation and relapse are sustained by a cell subset of Breast Cancer Stem Cells (BrCSCs). Here we show that miR-100 inhibits maintenance and expansion of BrCSCs in basal-like cancer through Polo-like kinase1 (Plk1) down-regulation. Moreover, miR-100 favors BrCSC differentiation, converting a basal like phenotype into luminal. It induces the expression of a functional estrogen receptor (ER) and renders basal-like BrCSCs responsive to hormonal therapy. The key role played by miR-100 in breast cancer free-survival is confirmed by the analysis of a cohort of patients' tumors, which shows that low expression of miR-100 is a negative prognostic factor and is associated with gene signatures of high grade undifferentiated tumors. Our findings indicate a new possible therapeutic strategy, which could make aggressive breast cancers responsive to standard treatments.