ZEB2 Drives Intra-tumor Heterogeneity and Skin Squamous Cell Carcinoma Formation with Distinct EMP Transition States

Overview

Journal iScience

Publisher Cell Press

Date 2024 Nov 18

PMID 39555401

Authors

Jeroen Verstappe

Nicolas Skrypek

Jordy De Coninck

Bieke Soen

Joachim Taminau

Marianthi Tatari

Kenneth Bruneel

Nele Loret

Kato De Clercq

Caroline Van den Broecke

Koen Van de Vijver

Jo Van Dorpe

Jody Haigh

Bram De Craene

Steven Goossens

Niels Vandamme

Geert Berx

Affiliations

Soon will be listed here.

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.

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