Identification of a core EMT signature that separates basal-like breast cancers into partial- and post-EMT subtypes

Erik Knutsen; Saikat Das Sajib; Tonje Fiskaa; James Lorens; Thorarinn Gudjonsson; Gunhild M Mælandsmo; Steinar Daae Johansen; Ole-Morten Seternes; Maria Perander

doi:10.3389/fonc.2023.1249895

Identification of a core EMT signature that separates basal-like breast cancers into partial- and post-EMT subtypes

Front Oncol. 2023 Dec 4:13:1249895. doi: 10.3389/fonc.2023.1249895. eCollection 2023.

Authors

Erik Knutsen^{1

2}, Saikat Das Sajib¹, Tonje Fiskaa¹, James Lorens³, Thorarinn Gudjonsson^{4

5}, Gunhild M Mælandsmo^{1

6}, Steinar Daae Johansen^{1

7}, Ole-Morten Seternes⁸, Maria Perander^{1

2}

Affiliations

¹ Department of Medical Biology, Faculty of Health Sciences, UiT the Arctic University of Norway, Tromsø, Norway.
² Centre for Clinical Research and Education, University Hospital of North Norway, Tromsø, Norway.
³ Department of Biomedicine, University of Bergen, Bergen, Norway.
⁴ Department of Anatomy, Faculty of Medicine, School of Health Sciences, University of Iceland, Reykjavik, Iceland.
⁵ Department of Hematology, Landspitali, University Hospital, Reykjavik, Iceland.
⁶ Department of Tumor Biology, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway.
⁷ Genomics Division, Faculty of Bioscience and Aquaculture, Nord University, Bodø, Norway.
⁸ Department of Pharmacy, Faculty of Health Sciences, UiT The Arctic University of Norway, Tromsø, Norway.

Abstract

Epithelial-mesenchymal transition (EMT) is a cellular plasticity program critical for embryonic development and tissue regeneration, and aberrant EMT is associated with disease including cancer. The high degree of plasticity in the mammary epithelium is reflected in extensive heterogeneity among breast cancers. Here, we have analyzed RNA-sequencing data from three different mammary epithelial cell line-derived EMT models and identified a robust mammary EMT gene expression signature that separates breast cancers into distinct subgroups. Most strikingly, the basal-like breast cancers form two subgroups displaying partial-EMT and post-EMT gene expression patterns. We present evidence that key EMT-associated transcription factors play distinct roles at different stages of EMT in mammary epithelial cells.

Keywords: EMT-transcription factors; RNA-Seq; breast cancer; epithelial-mesenchymal transition; gene expression signature.

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was supported by Northern Norway Regional Health Authority (HNF1418-18, HNF1585-21 and HNF1547-20). The publication charges for this article have been funded by a grant from the publication fund of UiT the Arctic University of Norway.