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Abstract
Tumor-initiating cells (TICs) drive tumor formation and may contribute to metastasis. Using a mouse model of squamous cell carcinoma (SCC), we identified two TIC populations: Hoechst dye-excluding side population (SP) and SP-/CD34+/CD49f+ cells. SP size correlated with lung metastasis and increased in passaged tumors. miRNA profiling revealed miR-9 upregulation in metastatic SP cells, promoting chemoresistance and invasion via Abcb1a regulation. In human HNSCC, miR-9 expression associated with metastatic node status in passaged tumors. Sox2 was elevated in SP-/CD34+/CD49f+ cells, inhibiting invasion, suggesting distinct roles for TIC subsets. These findings implicate miR-9 and Sox2 in TIC-driven metastasis.