By promoting cell differentiation, miR-100 sensitizes basal-like breast cancer stem cells to hormonal therapy
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Annalisa Petrelli1,*, Rosachiara Carollo2,*, Marilisa Cargnelutti1, Flora Iovino2, Maurizio Callari3, Daniela Cimino4, Matilde Todaro2, Laura Rosa Mangiapane2, Alessandro Giammona2, Adriana Cordova2, Filippo Montemurro1, Daniela Taverna4, Maria Grazia Daidone3, Giorgio Stassi2,* and Silvia Giordano1,*
1 University of Torino School of Medicine, Candiolo Cancer Institute-FPO, IRCCS, Str. Provinciale, Candiolo, Torino, Italy
2 Department of Surgical and Oncological Sciences, Cellular and Molecular Pathophysiology Laboratory, University of Palermo, Palermo, Italy
3 Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
4 Molecular Biotechnology Center (MBC), Department of Oncological Sciences, Center for Molecular Systems Biology, Via Nizza, University of Torino, Torino, Italy
* These authors contributed equally to this work
Silvia Giordano, email:
Giorgio Stassi, email:
Annalisa Petrelli, email:
Keywords: Breast cancer, basal-like, differentiation, miR-100
Received: September 30, 2014 Accepted: December 10, 2014 Published: December 11, 2014
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.
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