Verstappe Jeroen, Skrypek Nicolas, De Coninck Jordy, Soen Bieke, Taminau Joachim, Tatari Marianthi, Bruneel Kenneth, Loret Nele, De Clercq Kato, Van den Broecke Caroline, Van De Vijver Koen, Van Dorpe Jo, Haigh Jody, De Craene Bram, Goossens Steven, Vandamme Niels, Berx Geert
Molecular and Cellular Oncology Laboratory, Department of Biomedical Molecular Biology, Ghent University, Technologiepark 71, 9052 Ghent, Belgium.
Cancer Research Institute Ghent (CRIG), Ghent, Belgium.
iScience. 2024 Oct 16;27(11):111169. doi: 10.1016/j.isci.2024.111169. eCollection 2024 Nov 15.
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.
约5%的皮肤鳞状细胞癌（cSCC）患者预后较差，这与肿瘤分化丧失、侵袭和转移有关，所有这些都与上皮-间充质可塑性（EMP）过程相关。在此，我们表明，与EMP相关的转录因子ZEB2驱动cSCC异质性，其类似于双相癌肉瘤样肿瘤。单细胞RNA测序揭示了从完全上皮（E）到中间（EM）再到完全间充质（M）的不同亚群，这与细胞表面标志物EPCAM、CDH1、ITGB4和CD200的逐渐丧失有关。间充质特征与更高的转移能力和失巢凋亡抗性相关，但这伴随着对TNF诱导的细胞死亡的敏感性。我们共同提供了对cSCC异质性以及靶向间充质转移诱导细胞的模式的见解。
