Table 1.

Major functions of nicotine/α7nAChR in NSCLC development.

Functions	α7nAChR-Associated Signalling Pathways in NSCLC
Cell proliferation	α7nAChR enhances cell proliferation by activating retinoblastoma tumor suppressor protein-proto-oncogene, serine/threonine kinase (Rb-RAF-1) and Src pathways mediated by protein β-arrestin. α7nAChR causes activation of phosphatidylinositol-3 kinase/Akt (PI3K/Akt), Sp1 transcription factor/GATA binding protein (Sp1/GATA1) and the mammalian target of rapamycin (mTOR) signalling pathways, which enhance proliferation of NSCLC cells. α7nAChR activates signalling pathways of PI3K/Akt/Src, leading to upregulation of cyclinD1 expression in NSCLC cells. α7nAChR promotes cell proliferation by the activation of nicotine-induced vimentin and fibronectin expression through the Raf-1/extracellular signal-regulated kinase/mitogen-activated protein kinase (Raf-1/ERK/MAPK) signaling pathway.
Metastasis	α7nAChR stimulates migration and invasion of NSCLC cells by activating the ERK/MAPK, Src/protein kinase Cι/FAK (Src/PKCι/FAK), PI3K and Yes-associated protein-E2F transcription factors 1 (YAP-E2F1) signaling pathways.
Angiogenesis	Upregulation of α7nAChR in NSCLC cells promotes angiogenesis via activation of Ca2+ influx, which stimulates signaling pathways including VEGF-A, NF-κB, PI3K/AKT and FGFR2.
Anti-apoptosis	α7nAChR suppresses apoptosis in nicotine-induced NSCLC cells by activating the PI3K/Akt pathway, which inhibits proapoptotic Bcl-2-associated X protein (Bax) expression. Nicotine upregulates the protein expression of B-cell lymphoma-2 (Bcl-2) through α7nAChR-mediated activation of the Raf-1/MAPK signaling pathway, which leads to phosphorylation of transcription factor c-myc, resulting in significantly inhibited apoptosis in NSCLC cells.