CD9 knockdown inhibits cell proliferation, migration, and invasion and augments apoptosis in tongue cancer cells through regulation of the EGFR signalling pathway.

backgroundCancer comprises a group of diseases characterized by abnormal cell growth, forming malignant tumors that can invade nearby tissues and spread to other parts of the body. Owing to continuous exposure to environmental carcinogens, the oral cavity is a common site for malignant epithelial neoplasms in the head and neck region, with tongue cancer being particularly prevalent. Tongue cancer tends to exhibit aggressive behaviour, often resulting in recurrence and lymph and distant metastasis. CD9, a member of the tetraspanin family, plays a crucial role because of its membrane-dependent effects. Its biological activities include cell adhesion, motility, metastasis, growth, signal transduction and differentiation. METHODOLOGY: CD9 was overexpressed and knocked down in tongue cancer cells (SAS cells). Cell proliferation, migration, invasion, colony formation, and gene and protein expression analyses were performed. Protein-guided docking and normal mode analysis were performed to study the interaction between CD9 and EGFR.

resultsThe proliferation, migration, invasion and colony formation ability significantly increased in CD9 + + cells. The expression of EGFR, p-EGFR, Akt, p-Akt, Bcl2 and MMP1 also increased significantly in CD9 + + cells, whereas the expression of bak and caspase3 increased in CD9-KD cells. This finding implies that CD9 regulates the expression of EGFR. CD9 is crucial for the insertion of EGFR into the plasma membrane. Loss of CD9 decreases the number of EGFRs on the cell surface, thus attenuating the signalling pathway required for cancer progression.

conclusionAs CD9 is very important for the function of EGFR, targeting CD9 could be an alternative therapy in the context of chemoresistance to EGFR-targeted therapy.