Along with the acquisition of CICs phenotype and migrating/invasive properties, COPD-EVs treatment of HBEC-KRASV12high significantly up-regulated the expression of some stemness and mesenchymal genes, as Integrin-α6, fibronectin and SNAI2, with a concomitant down-modulation of E-cadherin (CHD1) compared to controls, indicating a possible induction of EMT (Fig. 3D and Supplementary Fig. S2A). This evidence concerns the gene SNAI2 and chronic obstructive pulmonary disease.