The Interplay of SMAD4 and EMT in Oral Squamous Cell Carcinoma

Background: Oral squamous cell carcinoma (OSCC) is a prevalent malignancy with a poor prognosis. Surgical removal of the primary tumor and regional lymph nodes (LNs) remains the fundamental treatment for OSCC, although 40% of patients are negative for LN metastasis. The epithelial-mesenchymal transition (EMT) plays a crucial role in OSCC progression by enabling epithelial cells to acquire mesenchymal traits, thereby facilitating migration and metastasis. Smad4, a tumor suppressor protein, is known to mediate EMT and is associated with poor prognosis and metastasis; however, its precise pro-metastatic role in OSCC via EMT remains unclear. Aims: We hypothesize that EMT and Smad4 could serve as practical diagnostic tools for personalized OSCC treatment. Methods: In this study, we analyzed 23 OSCC samples from Tzafon Medical Center, comparing the expression of Smad4 and EMT markers with clinical and histopathological data. Additionally, an OSCC cell model with and without Smad4 mutation was used to investigate tumor phenotypes, including proliferation and invasion, in relation to EMT markers. Results and Conclusion: Our findings reveal a strong correlation between EMT markers, Smad4 expression, and OSCC pathological staging, with the cell model further confirming the link between Smad4 and EMT markers. The combined influence of Smad4 and EMT markers on OSCC progression highlights their potential as diagnostic tools and as guides for personalized treatment strategies.