2. Academic Validation
  3. ETV7 regulates breast cancer stem-like cell features by repressing IFN-response genes

ETV7 regulates breast cancer stem-like cell features by repressing IFN-response genes

  • Cell Death Dis. 2021 Jul 27;12(8):742. doi: 10.1038/s41419-021-04005-y.
Laura Pezzè 1 2,  Erna Marija Meškytė 1 3,  Mattia Forcato 4,  Stefano Pontalti 1 5,  Kalina Aleksandra Badowska 1 2,  Dario Rizzotto 6 7,  Ira-Ida Skvortsova 8 9,  Silvio Bicciato 4,  Yari Ciribilli 10
Affiliations

Affiliations

  • 1 Laboratory of Molecular Cancer Research, Department of Cellular, Computational and Integrative Biology (CIBIO), University of Trento, Trento, Italy.
  • 2 Alia Therapeutics s.r.l., Trento, Italy.
  • 3 Department of Biological Models, Institute of Biochemistry, Life Sciences Centre, Vilnius University, Vilnius, Lithuania.
  • 4 Department of Life Sciences, University of Modena and Reggio Emilia, Modena, Italy.
  • 5 Azienda Provinciale per i Servizi Sanitari, APSS, Trento, Italy.
  • 6 Laboratory of Transcriptional Networks, Department CIBIO, University of Trento, Trento, Italy.
  • 7 CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria.
  • 8 EXTRO-Lab, Department of Therapeutic Radiology and Oncology, Medical University of Innsbruck, Innsbruck, Austria.
  • 9 Tyrolean Cancer Research Institute, Innsbruck, Austria.
  • 10 Laboratory of Molecular Cancer Research, Department of Cellular, Computational and Integrative Biology (CIBIO), University of Trento, Trento, Italy. yari.ciribilli@unitn.it.
PMID: 34315857 DOI: 10.1038/s41419-021-04005-y
Abstract

Cancer Stem Cells (CSCs) represent a population of cells within the tumor able to drive tumorigenesis and known to be highly resistant to conventional chemotherapy and radiotherapy. In this work, we show a new role for ETV7, a transcriptional repressor member of the ETS family, in promoting breast Cancer stem-like cells plasticity and resistance to chemo- and radiotherapy in breast Cancer (BC) cells. We observed that MCF7 and T47D BC-derived cells stably over-expressing ETV7 showed reduced sensitivity to the chemotherapeutic drug 5-fluorouracil and to radiotherapy, accompanied by an adaptive proliferative behavior observed in different culture conditions. We further noticed that alteration of ETV7 expression could significantly affect the population of breast CSCs, measured by CD44+/CD24low cell population and mammosphere formation efficiency. By transcriptome profiling, we identified a signature of Interferon-responsive genes significantly repressed in cells over-expressing ETV7, which could be responsible for the increase in the breast CSCs population, as this could be partially reverted by the treatment with IFN-β. Lastly, we show that the expression of the IFN-responsive genes repressed by ETV7 could have prognostic value in breast Cancer, as low expression of these genes was associated with a worse prognosis. Therefore, we propose a novel role for ETV7 in breast Cancer stem cells' plasticity and associated resistance to conventional chemotherapy and radiotherapy, which involves the repression of a group of IFN-responsive genes, potentially reversible upon IFN-β treatment. We, therefore, suggest that an in-depth investigation of this mechanism could lead to novel breast CSCs targeted therapies and to the improvement of combinatorial regimens, possibly involving the therapeutic use of IFN-β, with the aim of avoiding resistance development and relapse in breast Cancer.

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