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Figure 2. Mechanisms related to CSCs’ chemoresistance in HNSCC. Overexpression of Bmi1, Sox2, Sox8, Oct4, Slug, Snail, Nanog, and TSPAN1 genes leads to the acquisition of drug resistance and stemness, EMT, and metastasis. CSCs activate signaling pathways such as the NOTCH1, FGF2, and Wnt/β-catenin to promote chemoresistance and stemness. Increased expression of ABC transporters, mainly ABCG2, the activation of EMT, cell cycle deregulation, increased autophagy, and activation of epigenetic mechanisms, such as up-regulation of miR-10, are involved with CSC’s chemoresistance in HNSCC.