Partial-EMT in oral squamous cell carcinoma: molecular circuitry and clinical translation

Oral squamous cell carcinoma (OSCC) is a prevalent malignancy with high morbidity and mortality. Globally, about 400 000 people are affected, often with a poor quality of life. Its high mortality is mainly due to its aggressive growth and tendency to spread. Epithelial-mesenchymal transition (EMT) is a central regulatory hub driving tumor cell migration and invasion by enabling changes in cell characteristics. During EMT, epithelial cells gradually take on mesenchymal traits, gaining mobility and spreading more easily. Recent multi-omics studies show that many cancer cells exist in a hybrid or partial-EMT state, which lies between the full epithelial and mesenchymal forms. Cells in this state are especially invasive and metastatic, with high plasticity that promotes tumor progression. This review summarizes the role of partial-EMT in OSCC, with a focus on how it alters the tumor microenvironment (TME), promotes invasion and metastasis, and influences cancer stem cells (CSCs). We also highlight the link between partial-EMT and treatment resistance in OSCC. Based on these insights, we discuss therapeutic strategies targeting partial-EMT to improve outcomes. Targeting partial-EMT may offer promising strategies to enhance treatment effectiveness and improve patient survival and quality of life.