Human secreted protein SLURP-1 abolishes nicotine-induced proliferation, PTEN down-regulation and α7-nAChR expression up-regulation in lung cancer cells.

Human secreted protein SLURP-1 abolishes nicotine-induced proliferation, PTEN down-regulation and α7-nAChR expression up-regulation in lung cancer cells. Int Immunopharmacol. 2020 Feb 24;82:106303 Authors: Shulepko MA, Bychkov ML, Shlepova OV, Shenkarev ZO, Kirpichnikov MP, Lyukmanova EN Abstract Human Ly-6/uPAR-related protein-1 (SLURP-1) is an allosteric negative modulator of the α7-type nicotinic acetylcholine receptor (α7-nAChR), one of the key receptors promoting nicotine-induced proliferation of lung cancer cells. Incubation of lung adenocarcinoma A549 cells with recombinant SLURP-1 (rSLURP-1) at concentrations >10 nM resulted in the significant decrease of the cell growth (~70%), while treatment of normal lung-derived WI-38 fibroblasts with rSLURP-1 did not influence the cell proliferation up to 1 μM of the protein. rSLURP-1 fully abolished the nicotine-induced increase of the cell proliferation, down-regulation of the expression of PTEN (the negative regulator of the AKT pathway, controlling the growth, survival, and proliferation of cancer cells), and up-regulation of the α7-nAChR expression in the A549 cells. Using the siRNA against α7-nAChR and inhibitors of different cell-surface receptors, we showed that rSLURP-1 antiproliferative effect in A549 cells is connected with α7-nAChR, epidermal growth factor receptors, and β-adrenergic receptors. Moreover, we found that downstream effectors of rSLURP-1 are IP3 rec...
Source: International Immunopharmacology - Category: Allergy & Immunology Authors: Tags: Int Immunopharmacol Source Type: research