Specifically, Zhang et al. showed that nicotine induced pro-angiogenic effects by upregulating HIF-1α, and this effect was significantly attenuated by blocking the nAChR pathway, which consists of the Ca2+/calmodulin, Src, protein kinase C(PKC), PI3K-AKT, MAPK-ERK1/2 and mTOR pathways in NSCLC cell lines [100]. The gene discussed is CHRNA4; the disease is non-small cell lung carcinoma.