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

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

Risultato della ricerca: Articlepeer review

27 Citazioni (Scopus)

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
pagine (da-a)2315-2330
Numero di pagine16
RivistaOncotarget
Volume6
Stato di pubblicazionePublished - 2015

All Science Journal Classification (ASJC) codes

  • Oncology

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