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Barkovskaya A, Goodwin CM, Seip K, et al. Detection of phenotype-specific therapeutic vulnerabilities in breast cells using a CRISPR loss-of-function screen. Mol Oncol. 2021;15(8):2026-2045doi: 10.1002/1878-0261.12951.
Barkovskaya, A., Goodwin, C. M., Seip, K., Hilmarsdottir, B., Pettersen, S., Stalnecker, C., Engebraaten, O., Briem, E., Der, C. J., Moestue, S. A., Gudjonsson, T., Maelandsmo, G. M., & Prasmickaite, L. (2021). Detection of phenotype-specific therapeutic vulnerabilities in breast cells using a CRISPR loss-of-function screen. Molecular oncology, 15(8), 2026-2045. https://doi.org/10.1002/1878-0261.12951
Barkovskaya, Anna, et al. "Detection of phenotype-specific therapeutic vulnerabilities in breast cells using a CRISPR loss-of-function screen." Molecular oncology vol. 15,8 (2021): 2026-2045. doi: https://doi.org/10.1002/1878-0261.12951
Barkovskaya A, Goodwin CM, Seip K, Hilmarsdottir B, Pettersen S, Stalnecker C, Engebraaten O, Briem E, Der CJ, Moestue SA, Gudjonsson T, Maelandsmo GM, Prasmickaite L. Detection of phenotype-specific therapeutic vulnerabilities in breast cells using a CRISPR loss-of-function screen. Mol Oncol. 2021 Aug;15(8):2026-2045. doi: 10.1002/1878-0261.12951. Epub 2021 May 01. PMID: 33759347; PMCID: PMC8333781.
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Mol Oncol. 2021 Aug;15(8):2026-2045. doi: 10.1002/1878-0261.12951. Epub 2021 May 01.

Detection of phenotype-specific therapeutic vulnerabilities in breast cells using a CRISPR loss-of-function screen.

Molecular oncology

Anna Barkovskaya, Craig M Goodwin, Kotryna Seip, Bylgja Hilmarsdottir, Solveig Pettersen, Clint Stalnecker, Olav Engebraaten, Eirikur Briem, Channing J Der, Siver A Moestue, Thorarinn Gudjonsson, Gunhild M Maelandsmo, Lina Prasmickaite

Affiliations

  1. Department of Tumor Biology, Institute for Cancer Research, Oslo University Hospital, The Norwegian Radium Hospital, Oslo, Norway.
  2. Department of Circulation and Medical Imaging, Norwegian University of Science and Technology, Trondheim, Norway.
  3. Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, NC, USA.
  4. Biomedical Center, School of Health Sciences, University of Iceland, Reykjavik, Iceland.
  5. Department of Pathology, Landspitali University Hospital, Reykjavik, Iceland.
  6. Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Norway.
  7. Department of Oncology, Oslo University Hospital, Norway.
  8. Department of Genetics and Molecular Medicine, Landspitali University Hospital, Reykjavik, Iceland.
  9. Department of Health Sciences, Nord University, Bodø, Norway.
  10. Department of Laboratory Hematology, Landspitali University Hospital, Reykjavik, Iceland.
  11. Faculty of Health Sciences, Institute of Medical Biology, The Arctic University of Norway - University of Tromsø, Norway.

PMID: 33759347 PMCID: PMC8333781 DOI: 10.1002/1878-0261.12951

Abstract

Cellular phenotype plasticity between the epithelial and mesenchymal states has been linked to metastasis and heterogeneous responses to cancer therapy, and remains a challenge for the treatment of triple-negative breast cancer (TNBC). Here, we used isogenic human breast epithelial cell lines, D492 and D492M, representing the epithelial and mesenchymal phenotypes, respectively. We employed a CRISPR-Cas9 loss-of-function screen targeting a 2240-gene 'druggable genome' to identify phenotype-specific vulnerabilities. Cells with the epithelial phenotype were more vulnerable to the loss of genes related to EGFR-RAS-MAPK signaling, while the mesenchymal-like cells had increased sensitivity to knockout of G

© 2021 The Authors. Molecular Oncology published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.

Keywords: CRISPR knockout screen; actionable targets; epithelial-mesenchymal transition; phenotype plasticity; therapeutic vulnerabilities; triple-negative breast cancer

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