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Poster Display session 3

4357 - Identification of a stemness-related gene panel associated with BET inhibition in triple negative breast cancer

Date

30 Sep 2019

Session

Poster Display session 3

Topics

Translational Research

Tumour Site

Breast Cancer

Presenters

Eva Galan-Moya

Citation

Annals of Oncology (2019) 30 (suppl_5): v760-v796. 10.1093/annonc/mdz268

Authors

E.M. Galan-Moya1, M. Nuncia-Cantarero1, L. Serrano-Oviedo1, S. Morcillo-García1, C. Nieto-Jiménez2, M. Burgos2, B. Győrffy3, A. Ocaña4

Author affiliations

  • 1 Medical Sciences & Regional Center For Biomedical Research, University of Castilla-La Mancha, 02008 - Albacete/ES
  • 2 Oncología Traslacional, Complejo Hospitalario Universitario de Albacete, 02006 - Albacete/ES
  • 3 Institute Of Enzymology, MTA TTK Lendület Cancer Biomarker Research Group, Budapest/HU
  • 4 Drugs Development, Hospital Clínico San Carlos, 28040 - Madrid/ES

Resources

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Abstract 4357

Background

Triple negative breast cancers (TNBC) are enriched with cells bearing stem-like features (CSC), which underlie cancer progression, thus targeting stemness could be an interesting treatment approach. In turn, the epigenetic machinery is crucial for the maintenance of the stemness phenotype. The BET family of epigenetic readers are emerging as novel targets for cancer therapy and have shown preclinical effect in breast cancer. In this work we evaluate the effect of the BET inhibitor (BETi) JQ1 on stemness in TNBC.

Methods

Transcriptomic, functional annotation and qPCR studies were performed on JQ1-exposed TNBC cells. Results were confirmed on spheroids and spheroid-derived tumours. Limiting dilution assays, matrigel invasion experiments, immunofluorescence staining, and flow cytometry studies were also performed to evaluate the effect of JQ1 on CSC features. For the outcome analysis, the online tool Kaplan-Meier Plotter and an integrated response database were used.

Results

JQ1 can modify the expression of stemness-related genes incultured TNBC cells. Among these changes, the CD44/CD24 and ALDH1A1 expression, both classical stemness markers, were diminished by JQ1. Using a validated spheroid model, to mimic the intrinsic characteristics of CSCs, we show that JQ1 decreased surface expression of CD44, inhibited self-renewal and invasion, and induced cells arrest in G0/G1, therefore altering the stemness phenotype in TNBC. Four of the identified stemness genes, GJA1, CD24, EPCAM, and SOX9, were found to be associated with worse patient outcome in TNBC. Furthermore, ABCG2 and RUNX2 predicted low response to chemotherapy in TNBC patients.

Conclusions

In this work we show how BETi modify the stemness landscape in TNBC. Thus, we propose a novel role for JQ1 as a stemness-targeting drug. Loss of the stem cell phenotype via JQ1 treatment could lead to less aggressive and more chemo-sensitive tumours, which would reflect in better patient prognosis.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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