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bioRxiv · 10.1101/2020.10.20.346692

Partial epithelial-to-mesenchymal transition is prognostic and associates with Slug in head and neck cancer

Schinke, H.·Pan, M.·Akyol, M.·Kranz, G.·Libl, D.·Simon, F.·Canis, M.·Baumeister, P.·Gires, O.
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Abstract

Therapy resistance leading to local recurrence and metastases remains highly problematic in head and neck squamous cell carcinomas (HNSCC). Single cell RNA-sequencing defined a partial epithelial-to-mesenchymal transition (p-EMT) signature associated with metastases in HNSCC. However, the prognostic value of the p-EMT signature and potential drivers of p-EMT in HNSCC remain unclear. Here, single sample scoring of molecular phenotypes (Singscoring) served to establish clinical p-EMT-Singscores that were significantly associated with nodal metastases and predicted overall survival in two independent HNSCC cohorts. p-EMT-Singscores correlated most strongly with EMT transcription factor (EMT-TF) Slug. In vitro, Slug promoted p-EMT, enhanced invasion, and resistance to irradiation. In patients, Slug protein levels in tumors predicted disease-free survival and its peripheral expression at the interphase to tumor-microenvironment was significantly increased in recurring patients. Thus, p-EMT represents a novel clinical risk-predictor that impacts on HNSCC patients outcome and is partly controlled by Slug.

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Schinke, H., Pan, M., Akyol, M., Kranz, G., Libl, D., Simon, F., Canis, M., Baumeister, P., Gires, O.. 2020-10-21. Partial epithelial-to-mesenchymal transition is prognostic and associates with Slug in head and neck cancer. https://doi.org/10.1101/2020.10.20.346692

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