Figure 1: A schematic of nAChR-mediated regulation of diverse tumorigenic processes. nAChRs are activated by tobacco smoke components like NNN, NNK, and nicotine with different affinity. Induced nAChRs activate several downstream signaling pathways involved in cell proliferation, inhibition of apoptosis, metastasis, and angiogenesis in a variety of cancer and primary cells. Agonist binding to nAChR forms complex with β-arrestin and Src and results in Raf-1 activation. Activated Raf-1 phosphorylates and inactivates Rb tumor-suppressor-function. These in turn results in E2F-1-mediated transcriptional upregulation of target genes involved in cell proliferation, angiogenesis, and inhibition of apoptosis. Downstream effect of nAChR activation is also indirectly supported by the activation of β-adrenergic receptor (β-AR) signaling. Nicotine exposure directly results in metastatic dissemination of primary tumor by inducing epithelial to mesenchymal transition (EMT) in cancer cells.