The Clinical Relevance of Epithelial-to-Mesenchymal Transition Hallmarks - A Cut-Off-Based Approach in Healthy and Cancerous Cell Lines

Sep 23, 2026

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Atypical epithelial-to-mesenchymal transition (EMT) activation drives cancer cell dissemination by enabling epithelial tumor cells to detach from primary masses and gain survival advantages in circulation. EMT is described as a continuum producing diverse subpopulations with concurrent epithelial and mesenchymal marker expression. The study examines EMT-related gene panels across healthy, primary, metastatic, and tissue-derived mesenchymal cell lines to identify cut-off values reflecting cancer aggressiveness. CDH1, CDH5, and ZEB1 distinguish primary from metastatic cells, suggesting a tissue-specific progression signature and highlighting marker utility for aggressiveness and therapeutic responsiveness.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages20

Reading Time50 min

AccessFree to download

Introduction

EMT in physiology and pathology

EMT mechanisms and cancer metastasis

Results

Cut-off-based discrimination of cell types

Tissue-specific EMT marker signatures

Discussion

Clinical relevance of EMT markers

Implications for aggressiveness and therapy responsiveness

Article The Clinical Relevance of Epithelial-to-Mesenchymal Transition Hallmarks: A Cut-Off-Based Approach in Healthy and Cancerous Cell Lines Maria Cristina Rapanotti 1,*, Elisa Cugini 1,2, Maria Giovanna Scioli 1, Tonia Cenci 1, Silvia Anzillotti 1, Martina Puzzuoli 1, Alessandro Terrinoni 2,3, Amedeo Ferlosio 1, Anastasia De Luca 4, *,† and Augusto Orlandi 1,† Academic Editor: Emanuela Chiarella Received: 24 February 2025 Revised: 1 April 2025 Accepted: 8 April 2025 Published: 11 April 2025 Citation: Rapanotti, M.C.; Cugini, E.; Scioli, M.G.; Cenci, T.; Anzillotti, S.; Puzzuoli, M.; Terrinoni, A.; Ferlosio, A.; De Luca, A.; Orlandi, A. The Clinical Relevance of Epithelial-toMesenchymal Transition Hallmarks: A Cut-Off-Based Approach in Healthy and Cancerous Cell Lines. Int. J. Mol. Sci. 2025, 26, 3617. [https://doi.org/](https://doi.org/)[ ](https://doi.org/)[10.3390/ijms26083617](10.3390/ijms26083617) Copyright: © 2025 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ([https://creativecommons.org/](https://creativecommons.org/)[ ](https://creativecommons.org/)[licenses/by/4.0/](licenses/by/4.0/)) . 1 Anatomic Pathology, Department of Integrated Care Processes, University of Rome Tor Vergata, Viale Oxford 81, 00133 Rome, Italy; [scioli@med.uniroma2.it](scioli@med.uniroma2.it) (M.G.S.); [tonia.cenci@gmail.com](tonia.cenci@gmail.com) (T.C.); [anzillottisilvia@gmail.com](anzillottisilvia@gmail.com) (S.A.); [martina.puzzuoli@gmail.com](martina.puzzuoli@gmail.com) (M.P.); [ferlosio@med.uniroma2.it](ferlosio@med.uniroma2.it) (A.F.); [orlandi@uniroma2.it](orlandi@uniroma2.it) (A.O.) 2 Department of Laboratory Medicine, Tor Vergata University Hospital, 00133 Rome, Italy; [alessandro.terrinoni@uniroma2.it](alessandro.terrinoni@uniroma2.it) 3 Department of Experimental Medicine, University of Rome Tor Vergata, Via Montpellier 1, 00133 Rome, Italy 4 Department of Biology, University of Rome Tor Vergata, Via della Ricerca Scientifica 1, 00133 Rome, Italy * [Correspondence: mariacristina.rapanotti@ptvonline.it](Correspondence: mariacristina.rapanotti@ptvonline.it) (M.C.R.); [anastasia.deluca@uniroma2.it](anastasia.deluca@uniroma2.it) (A.D.L.)† These authors contributed equally to this work. Abstract: The atypical activation of the epithelial-to-mesenchymal transition represents oneof the main mechanisms driving cancer cell dissemination. It enables epithelial cancer cells to detach from the primary tumor mass and gain survival advantages in the bloodstream, significantly contributing to the spread of circulating tumor cells. Notably, epithelial-tomesenchymal transition is not a binary process but rather leads to the formation of a wide range of cell subpopulations characterized by the simultaneous expression of both epithelial and mesenchymal markers. Therefore, analyzing the modulation of EMT hallmarks during the conversion from healthy cells to metastatic cancer cells, which acquire stem mesenchymal characteristics, is of particular interest. This study investigates the expression of a panel of epithelial-to-mesenchymal transition-related genes in healthy cells, primary and metastatic cancer cells, and in mesenchymal cell lines, derived from various tissues, including the lung, colon, pancreas, skin, and neuro-ectoderm, with the aim of identifying potential cut-off values for assessing cancer aggressiveness. Interestingly, we found that the expression levels of CDH1, which encodes the epithelial marker E-cadherin, CDH5, encoding vascular endothelial cadherin, and the epithelial-to-mesenchymal transitiontranscription factor ZEB1, effectively distinguished primary from metastatic cancer cells. Additionally, our data suggest a tissue-specific signature in the modulation of epithelial-tomesenchymal transition markers during cancer progression. Overall, our results underscore

FAQs

Why is epithelial-to-mesenchymal transition important in cancer progression?

EMT enables epithelial cancer cells to detach from the primary tumor, gain survival advantages in the bloodstream, and increase aggressiveness, motility, and invasiveness, supporting metastasis formation.

Is EMT treated as a binary switch in the study?

No. EMT is presented as a non-binary process that generates a spectrum of cell subpopulations expressing both epithelial and mesenchymal markers simultaneously.

Which markers does the study report as distinguishing primary from metastatic cancer cells?

The expression levels of CDH1 (E-cadherin), CDH5 (vascular endothelial cadherin), and the EMT transcription factor ZEB1 effectively distinguish primary from metastatic cancer cells.

Sep 23, 2026

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