Introduction Cancer stem cells (CSCs) are considered the population of cells within the tumour able to drive tumorigenesis and known to be highly resistant to conventional chemotherapy. ETV7 is a poorly studied transcription factor member of ETS large family, known to be an interferon-stimulated gene. It has been recently found over-expressed in breast cancer (BC), with higher expression levels in the more aggressive BC subtypes. In this work, we investigated the effects of ETV7 increased expression on breast CSCs population and resistance to chemotherapy in BC cells. Material and methods We generated MCF7 and T47D BC-derived cells stably over-expressing ETV7 and obtained ETV7 KO in MDA-MB-231 BC cells using CRISPR/Cas9 technology. We analysed breast CSCs content via CD44/CD24 staining and FACS analysis, as well as mammospheres formation assay. We measured expression of ABC transporters and anti-apoptotic proteins via RT-qPCR and western blot. We finally assessed sensitivity to Doxorubicin and 5-Fluorouracil (5-FU) via MTT assay and AnnexinV/PI staining at FACS. Results and discussions We observed that the expression of ETV7 could be induced by various stimuli, particularly by chemotherapeutic drugs able to induce DNA damage. We then analysed the impact of ETV7 expression on the sensitivity to Doxorubicin and 5-FU and we could observe a significantly decreased sensitivity to these drugs upon ETV7 over-expression. We could also appreciate an increase in ABC transporters and BCL2 anti-apoptotic protein expression following ETV7 over-expression. We further observed that alteration of ETV7 expression could significantly affect the population of breast cancer stem cells (CD44+/CD24low cells) in different BC cell lines. Conclusion We propose a novel role for ETV7 in breast cancer stem cells plasticity and associated resistance to conventional chemotherapy. We finally suggest that an in-depth investigation of this mechanism could lead to novel breast CSCs targeted therapies and to the improvement of combinatorial regimens with the aim of avoiding resistance and relapse in breast cancer
