ZEB2 drives intra-tumor heterogeneity and skin squamous cell carcinoma formation with distinct EMP transition states

About 5% of patients with cutaneous squamous cell carcinoma (cSCC) have a poor prognosis which is associated with a loss of tumor differentiation, invasion and metastasis, all of which are linked to the process of epithelial-to-mesenchymal plasticity (EMP). Here, we showed that the EMP-associated transcription factor ZEB2 drives cSCC heterogeneity which resembles biphasic carcinosarcoma-like tumors. Single cell RNA sequencing revealed distinct subpopulations ranging from fully epithelial (E) to intermediate (EM) to fully mesenchymal (M), associated with the gradual loss of cell surface markers EPCAM, CDH1, ITGB4, and CD200. Mesenchymal features were associated with a higher metastatic capacity and anoikis resistance, yet this comes with a sensitivity toward TNF-induced cell death. Altogether we provide insights in cSCC heterogeneity and modes to target mesenchymal-metastasis inducing cells.

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Publication Details

Journal
iScience
Published
2024-10-16
DOI
https://doi.org/10.1016/j.isci.2024.111169
Citations
1
Primary Topic
Cancer Cells and Metastasis
Type
article
Field-Weighted Citation Impact
0.28

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article

ZEB2 drives intra-tumor heterogeneity and skin squamous cell carcinoma formation with distinct EMP transition states

Marianthi Tatari, Caroline Van den Broecke, Steven Goossens, Niels Vandamme et al.
1 citations
iScience
Cancer Cells and Metastasis
0.28
article

ZEB2 drives intra-tumor heterogeneity and skin squamous cell carcinoma formation with distinct EMP transition states

Marianthi Tatari, Caroline Van den Broecke, Steven Goossens, Niels Vandamme, Koen Van de Vijver, Bieke Soen, Jordy De Coninck, Joachim Taminau, Kenneth Bruneel, Geert Berx, Jo Van Dorpe, Jeroen Verstappe, Bram De Craene, Nele Loret, Kato De Clercq, Jody J. Haigh, Nicolas Skrypek
article en
1 citations

Abstract

About 5% of patients with cutaneous squamous cell carcinoma (cSCC) have a poor prognosis which is associated with a loss of tumor differentiation, invasion and metastasis, all of which are linked to the process of epithelial-to-mesenchymal plasticity (EMP). Here, we showed that the EMP-associated transcription factor ZEB2 drives cSCC heterogeneity which resembles biphasic carcinosarcoma-like tumors. Single cell RNA sequencing revealed distinct subpopulations ranging from fully epithelial (E) to intermediate (EM) to fully mesenchymal (M), associated with the gradual loss of cell surface markers EPCAM, CDH1, ITGB4, and CD200. Mesenchymal features were associated with a higher metastatic capacity and anoikis resistance, yet this comes with a sensitivity toward TNF-induced cell death. Altogether we provide insights in cSCC heterogeneity and modes to target mesenchymal-metastasis inducing cells.

iScienceVol. 27(11)
Ghent University Hospital (BE), The Netherlands Cancer Institute (NL), Ghent University (BE), CancerCare Manitoba (CA), Antwerp University Hospital (BE), Oncode Institute (NL), Cancer Research Institute Ghent (BE), VIB-UGent Center for Inflammation Research (BE), AZ Sint-Lucas (BE), Research Institute in Oncology and Hematology (CA), VIB Single Cell Core, University of Manitoba (CA)
Fonds Wetenschappelijk Onderzoek, Universiteit Gent, Stichting Tegen Kanker, Kom op tegen Kanker, Bijzonder Onderzoeksfonds UGent
Openalex Percentile: Top 35%
Cancer Cells and Metastasis
0.28
DOIOpen Access PDFOpenAlex
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