Kuo MH, Lee AC, Hsiao SH, et al. - Researchers evaluated how EGFR-TKI tolerance and lung cancer dissemination are influenced by cancer cell plasticity regulated by SOX2 and TGF-β signaling. Researchers describe that lung cancer cell plasticity and TKI tolerance are impacted by crosstalk between SOX2 and TGF-β signaling. Lung cancer cells showing mesenchymal morphology with deficient SOX2 expression was favored by TKI therapy, while promotion of TKI sensitivity as well as inhibition of mesenchymal phenotype was induced by SOX2 expression. SOX2 expression and TKI sensitivity were reduced by preselection of EGFR-mutant lung cancer cells with the mesenchymal phenotype, while SOX2 silencing not only induced vimentin but also it suppressed BCL2L11 expression and promoted TKI tolerance. Compared to SOX2-negative lung cancer cells, SOX2-positive lung cancer cells showed a lower dissemination capacity. Survival outcomes were worse in patients carrying EGFR mutations relative to to tumors expressing low SOX2 and high vimentin signature.