Fig. 6. RANK activated calcineurin/NFATC1 axis by STIM1-mediated Ca²⁺ influx.

a, b The calcium-flux analysis in response to ionomycin in CRC cells with RANK overexpression or knockdown. Besides, the effect of 100 μM 2APB on RANK-overexpressing SW480 and Caco2 cells were analyzed. c, d Western blotting showed that STIM1 protein levels were regulated by RANK in CRC cells. e STIM1 was co-stained with RANK in CRC tissue and paired normal colon tissues by immunofluorescence. The white arrowheads indicate that the overlap of RANK-positive cells and STIM1-positive CRC tissues. DAPI staining for nuclei. Scales bars = 50 μm. T human CRC tissues, N paired normal colorectal tissues. f–h The mRNA levels of STIM1 were positively correlated with NFATC1 in CRC assessed by online databases. i Silence of STIM1 reversed RANK-induced ACP5 expression activation and increased phosphorylated NFATC1. j, k Silence of STIM1 rescued the migration and invasion of RANK-overexpressing SW480 and Caco2 cells. Scales bars = 100 μm. Data are mean ± SD (n = 3). **P < 0.01, ***P < 0.001, ****P < 0.0001.