Nicotinic Receptors and Calcium Channels in Small Cell Lung Carcinoma: Functional Role, Modulation, and Autoimmunity^a

α7-Nicotinic Acetylcholine Receptors Affect Growth Regulation of Human Mesothelioma Cells

“…In PC12 cells, a Ca 2ϩ influx induced by carbachol, via nicotinic receptors, activates PYK2 tyrosine kinase, which in turn is responsible for triggering the Ras/ MAPK signaling cascade (25,26). However, the activation of MAPK in the SCLC cell line GLC-8 did not involve PYK2 tyrosine kinase activity (7). Nevertheless, PC12 also showed that Ca 2ϩ activates protein kinase C, thereby eliciting the MAPK cascade, initially by serine/threonine phosphorylation and thus activating RAF, which in turn causes phosphorylation and activation of MAP/ERK kinase, MAPK, cAMP-responsive element binding protein kinase, and cAMP-responsive element binding protein (32).…”

Development of Novel Therapeutic Strategies for Lung Cancer: Targeting the Cholinergic System

“…In addition to the agonist/competitive antagonist binding site, various interaction sites have been identified on nAChRs for non-competitive inhibitors [31] as well as for allosteric modulators [31]. In the last five years, the resolution of crystallographic structures of a protein homologous to the extracellular domain of nAChRs, the acetylcholine binding protein (AChBP) alone or complexed with various ligands [32][33][34][35][36][37][38] and refined electronic microscopy images of muscular receptor [39][40][41] in addition with numerous biochemical studies on the ligand binding sites, allowed to well understanding how various ligands interact on different nAChRs and revealed at the molecular level, the fundamental motion underlying the receptor activation (3). Finally, the region that lies at the interface between the extracellular ligand-binding site and the transmembrane channel domain and more precisely, some key residues of this region, have been identified for their critical role in the coupling between agonist binding and channel opening, allowing to better understand the structural machinery that links ligand binding to channel gating [42][43][44][45].…”

“…Afterward, the expression of ACh, AChE, and cholinergic receptors in non-neuronal cells was reported in several studies [3][4][5][6][7][8][9][10][11][12][13][14][15][16]. Indeed, recent data reported that SCLC expresses a cholinergic autocrine loop that can regulate cell growth.…”

Nicotine induces cell proliferation by -arrestin-mediated activation of Src and Rb-Raf-1 pathways

“…It has been shown that nicotine can induce calcium channels and activate Src in neuronal as well as certain non-neuronal cells (29,30); it has also been suggested that EGFR contributes to nAChR signaling (17). The contribution of these molecules to nicotine-induced proliferation of NSCLC cells was examined by BrdU incorporation ( Figure 3A).…”