Fig 2: NCX1 coordinates with TRPC1 to promote proliferation and migration of human GC cells. Summary data showing the inhibitory effects of either KB-R7943 (KB-R, 1 µM in MKN45, 4 µM in AGS, 8 µM in SGC7901), SKF96365 (SKF, 1 µM) or KB-R plus SKF on CaCl2 (1 mM)-enhanced proliferation (A–C) and migration (G–I) of GC cells. D–F, J–L Summary data showing the inhibitory effect of either shNCX1, SKF96365 (SKF, 1 µM) or shNCX1 plus SKF on CaCl2 (1 mM)-enhanced proliferation and migration of GC cells. Scale bar = 200 µm for each image. (*P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001, n = 3; ns, no significant differences).

Fig 3: Comparison of protein expression between the base (B) and apex (A) of the left ventricular epicardium in humans. Protein samples from the base (B) and the apex (A) of the LV epicardium were obtained from 3 men, 3 women, and 3 postmenopausal women and were probed with antibodies to compare the relative expression of Cav1.2a, NCX1, SERCA2a, RyR2, Nav1.5, and hERG. Panel a shows the protein densities which were normalized with respect to GAPDH. Panel b is a histogram of normalized band intensities expressed as base-apex percent differences derived from an analysis of myocardium from 6 men, 11 women, and 6 postmenopausal women

Fig 4: TRPC1/NCX1 coupling induces AKT phosphorylation and promotes GC growth and metastasis.A, D Inhibitory effects of either KB-R7943 (KB-R, 1 µM in MKN45, 8 µM in SGC7901), SKF96365 (SKF, 1 µM) or KB-R plus SKF on CaCl2 (2 mM)-induced AKT phosphorylation in GC cells. B, E Inhibitory effects of SKF, shNCX1 or shNCX1 plus SKF on CaCl2 (2 mM)-induced AKT phosphorylation in GC cells. C, F Inhibitory effects of either KB-R, shTRPC1 or shTRPC1 plus KB-R on CaCl2-induced AKT phosphorylation in GC cells. CaCl2 promoted growth of xenografted gastric tumors (G), which was attenuated by either KB-R7943 (H) or shNCX1 (I). J Inhibitory effects of shNCX1 on CaCl2-induced gastric tumor metastasis. K Immunohistochemical analysis and histological examination on expression of NCX1 and Ki67 proteins with or without NCX1 knockdown in GC tissues. Scale bar = 100 µm for each image. L, M Summary data comparing expression of NCX1 and Ki67 proteins analyzed by immunohistochemistry between with or without NCX1 knockdown in GC tissues. (*P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001, n = 3; ns, no significant differences). N The proposed oncogenic mechanisms of TRPC1/NCX1 coupling via Ca2+/AKT/ß-catenin pathway in Hp-associated GC.

Fig 5: CaCl2, Hp and virulence factors enhance NCX1 expression in human GC cells.A, G, M Representative time courses of CaCl2 (2 mM)-enhanced NCX1 protein expression in GC cells. Inhibitory effect of KB-R7943 (KB-R, 1 µM in MKN45, 4 µM in AGS, 8 µM in SGC7901) (B, H, N) or shNCX1 (C, I, O) on CaCl2 (2 mM)-enhanced NCX1 expression in GC cells. D, J, P Representative time courses of NH4Cl (2 mM)-enhanced NCX1 protein expression in GC cells. Inhibitory effect of KB-R7943 (E, K, Q) or shNCX1 (F, L, R) on NH4Cl (2 mM)-enhanced NCX1 protein expression in GC cells. S, T, U Representative time courses LPS (10 ng/ml)-enhanced NCX1 protein expression in GC cells. V, W Representative time courses H. pylori-enhanced NCX1 protein in GC cells. (*P < 0.05, **P < 0.01, ***P < 0.001, n = 3; ns, no significant differences).