Int J Oral Biol.  2026 Mar;51(1):1-8. 10.11620/IJOB.2026.51.1.1.

Cooperative promotion of epithelial-mesenchymal transition by TGF-β1 and EGF co-stimulation in oral squamous cell carcinoma cells

• Keum BR
• Heo SC
• Kim HJ

• KMID: 2583881
• DOI: http://doi.org/10.11620/IJOB.2026.51.1.1

Abstract

Epithelial-mesenchymal transition (EMT) is a critical process that drives tumor invasion and metastasis in oral squamous cell carcinoma (OSCC). Although transforming growth factor beta 1 (TGF-β1) and epidermal growth factor (EGF) are well-established inducers of EMT, the signaling crosstalk underlying their combined effects during the initial phase remains poorly defined. This study investigated the impact of combined TGF-β1 and EGF stimulation on EMTrelated phenotypic and molecular changes in HSC-3 OSCC cells. The cells were treated with TGF-β1 (10 ng/mL) and EGF (100 ng/mL), either individually or in combination. Cell proliferation, morphological changes, EMT marker expression, signaling pathway activation, and migratory capacity were assessed using cell counting kit-8 assays, quantitative morphological analysis, RT-qPCR, immunoblotting, and wound healing assays, respectively. Although TGF-β1 or EGF alone induced partial EMT-like changes, combined stimulation produced a pronounced spindleshaped morphology, an increased cell aspect ratio, and loss of epithelial cell-cell contact. Consistently, cotreatment led to greater repression of E-cadherin and enhanced upregulation of N-cadherin and Vimentin compared with single treatments. Notably, dual exposure markedly increased Smad2 and extracellular signal-regulated kinase (ERK) phosphorylation while accelerating cell migration. These findings indicate that TGF-β1 and EGF cooperatively promote EMT and migratory behavior through the coordinated activation of Smad2 and MAPK/ERK signaling pathways, highlighting this crosstalk as a potential therapeutic target for OSCC metastasis.

Keyword

Oral squamous cell carcinoma; Epithelial-mesenchymal transition; Transforming growth factor beta; Epidermal growth factor; Cell migration