The Src family kinase inhibitor drug Dasatinib and glucocorticoids display synergistic activity against tongue squamous cell carcinoma and reduce MET kinase activity

Sep 23, 2026

Aggressive tongue squamous cell carcinoma (TSCC) requires new therapeutic targets because prognosis remains poor and treatment choices are limited. This study evaluates protein tyrosine kinases, emphasizing Src family kinases (SFK), and investigates how the SFK inhibitor Dasatinib cooperates with clinically used glucocorticoids to suppress TSCC progression and signaling.

LanguageEnglish

CategoryHealthcare

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Pages20

Reading Time50 min

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Abstract

Background

Methods

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Introduction

Hmedat etal. Cell Communication and Signaling (2025) 23:293 [https://doi.org/10.1186/s12964-025-02129-8](https://doi.org/10.1186/s12964-025-02129-8) Cell Communication and Signaling RESEARCH Open Access The Src family kinase inhibitor drug Dasatinib and glucocorticoids display synergistic activity against tongue squamous cell carcinoma and reduce MET kinase activity Ali N. A. Hmedat 1,2, Jessica Doondeea3, Daniel Ebner4, Stephan M. Feller 1 and Marc Lewitzky1* Abstract Background Tongue squamous cell carcinoma (TSCC) is an aggressive cancer associated with a poor prognosis and limited treatment options, necessitating new drug targets to improve therapeutic outcomes. Our current work studies protein tyrosine kinases as well-known targets for successful cancer therapies. It focuses on Src family kinases (SFK), which are known to play a critical role in some head and neck tumors. Methods Western blot analyses of phospho-tyrosine protein patterns in 34 TSCC lines facilitated the investigation of SFK as contributors to these phosphorylations. The SFK inhibitors PP2 and Dasatinib were utilized to determine SFK contributions to cell motility and survival. A high-throughput screen with 1600 FDA-approved drugs was performed with three TSCC lines to discover drugs that act synergistically with Dasatinib against TSCC cell viability. Glucocorticoids emerged as potential candidates and were further investigated in 2D culture and by 3D soft agar colony formation. Dexamethasone was chosen as the major tool for our analyses of synergistic effects of Dasatinib and glucocorticoids onTSCC lines. Effects on the cell cycle were investigated by flow cytometry and expression levels of cell cycle regulators. Senescence was analyzed by senescence-associated β galactosidase detection and p27Kip1 protein expression. Autophagy was measured by Acridine Orange staining. Results A panel of 34 TSCC lines showed a surprisingly homogenous pTyr-protein pattern and a prominent 130 kDapTyr-protein. Inhibition of SFK activity greatly reduced overall pTyr-protein levels and p130Cas tyrosine phosphorylation. It also impaired TSCC viability in 2D cell culture and 3D soft agar colony formation. A high-throughput drug combination screen with Dasatinib identified glucocorticoids as promising candidates for synergistic activity. Dasatinib and Dexamethasone combination treatment showed strong synergistic effects on Src and p130Cas phosphorylation and led to reduced p130Cas expression. Dexamethasone also suppressed phosphorylation of the MET kinaseand its key substrate Gab1 . On the cellular level, Dasatinib combination with glucocorticoids led to G1 cell cycle arrest, appeared to increase senescence and enhanced autophagy. This was also reflected by effects on cell cycle regulatory proteins, including CDKs and cyclins. Conclusion This work is the first to show a strong synergistic activity of Dasatinib in combination with clinically used glucocorticoids in solid tumors. Furthermore, the tyrosine kinase MET and its effector protein Gab1 are newly *Correspondence: Marc Lewitzky [marc.lewitzky@uk-halle.de](marc.lewitzky@uk-halle.de) Full list of author information is available at the end of the article © The Author(s) 2025. Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in t

FAQs

Why is new therapy needed for tongue squamous cell carcinoma (TSCC)?

TSCC is described as aggressive with poor prognosis and limited treatment options, creating a need for new drug targets to improve outcomes.

How was Src family kinase (SFK) involvement in TSCC investigated?

The study used Western blot analysis of phospho-tyrosine patterns across 34 TSCC lines and applied SFK inhibitors PP2 and Dasatinib to assess effects on cell motility, survival, and phosphorylation states.

What key synergy was found between Dasatinib and glucocorticoids?

A high-throughput combination screen identified glucocorticoids as synergistic with Dasatinib. Dasatinib plus dexamethasone strongly enhanced inhibition of Src and p130Cas phosphorylation, suppressed MET phosphorylation, and led to functional effects such as G1 arrest, increased senescence, and enhanced autophagy.

Sep 23, 2026

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