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

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

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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.
Lingua originaleEnglish
Numero di pagine16
RivistaOncoTargets and Therapy
VolumeVol 5, No 24
Stato di pubblicazionePublished - 2014

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All Science Journal Classification (ASJC) codes

  • Oncology

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Todaro, M., Stassi, G., Cordova, A., Giammona, A., Mangiapane, L. R., Callari, M., Cargnelutti, M., Montemurro, F., Cimino, D., Petrelli, A., Taverna, D., Daidone, M. G., & Giordano, S. (2014). By promoting cell differentiation, miR-100 sensitizes basal-like breast cancer stem cells to hormonal therapy. OncoTargets and Therapy, Vol 5, No 24.