TY - JOUR
T1 - By promoting cell differentiation, miR-100 sensitizes basal-like breast cancer stem cells to hormonal therapy
AU - Cordova, Adriana
AU - Todaro, Matilde
AU - Mangiapane, Laura Rosa
AU - Stassi, Giorgio
AU - Giammona, Alessandro
AU - Callari, Maurizio
AU - Cargnelutti, Marilisa
AU - Montemurro, Filippo
AU - Cimino, Daniela
AU - Carollo, Rosachiara
AU - Giammona, Alessandro
AU - Mangiapane, Laura Rosa
AU - Cordova, Adriana
AU - Petrelli, Annalisa
AU - Taverna, Daniela
AU - Stassi, Giorgio
AU - Todaro, Matilde
AU - Daidone, Maria Grazia
AU - Giordano, Silvia
AU - Iovino, Flora
PY - 2015
Y1 - 2015
N2 - 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.
AB - 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.
UR - http://hdl.handle.net/10447/103963
M3 - Article
SN - 1949-2553
VL - 6
SP - 2315
EP - 2330
JO - Oncotarget
JF - Oncotarget
ER -