By promoting cell differentiation, miR-100 sensitizes basal-like breast cancer stem cells to hormonal therapy.

Annalisa Petrelli, Rosachiara Carollo, Marilisa Cargnelutti, Flora Iovino, Maurizio Callari, Daniela Cimino, Matilde Todaro, Laura Rosa Mangiapane, Alessandro Giammona, Adriana Cordova, Filippo Montemurro, Daniela Taverna, Maria Grazia Daidone, Giorgio Stassi, Silvia Giordano

Index: Oncotarget 6(4) , 2315-30, (2015)

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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.