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.
Highlights
The onset and progression of malignant tumors depend on a small pool of tumor cells with biological properties similar to those of normal adult stem cells
MiR-100 down-regulation induces a mammosphere-like phenotype in breast cancer cells
The breast cancer cell line MCF7 was transiently transfected in the absence of serum, either with a miR-100 specific antagomir or a control antagomir
Summary
The onset and progression of malignant tumors depend on a small pool of tumor cells with biological properties similar to those of normal adult stem cells. In accordance to this cancer stem cell hypothesis, tumors are organized in a hierarchical manner and are characterized by cells that exhibit the ability to self-renew as well as to give rise to differentiated cells. CSCs are thought to possess intrinsic resistance to current conventional therapies as compared to the bulk tumor cell population and it has been proposed that tumor recurrence is driven by this subpopulation of CSCs [3,4,5]
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