Fig. 1: NALCN loss-of-function in aggressive cancers.
From: The NALCN channel regulates metastasis and nonmalignant cell dissemination
a, Differential gene expression between normal PROM1+ gastric cells and P1KP-GAC cells (downregulated ion channels are highlighted). Benjamini–Hochberg corrected P value, alpha = 0.05. b, Nalcn RNA in situ hybridization and Prom1 expression (β-galactosidase (LacZ)) in Prom1CreERT2/LacZ mouse stomach (n = 3 biological replicates, 10 fields each; upper) and P1KP-GAC (n = 3 biological replicates, 10 fields each; lower). Numbers are shown as mean ± s.e.m. Prom1+/Nalcn+ cells. Scale bar, 50 μm. c, t-SNE plot of 10,022 human cancers (P value, dN/dS shown; Source data). d, Mutant residues enriched in NALCN pore turret (blue) and voltage-sensing (red) domains. P = 0.0275; permuted P value for probability of observing two clusters of 20 and 25 residues. e, Impact of 196 NALCN mutations on selectivity filter radius determined by HOLE analysis. f, NALCN pore closure by NALCN mutations in stage I (n = 47), stage II (n = 73), stage III (n = 74) and stage IV (n = 27) human cancers. Two-tailed Mann–Whitney U-test: stage I versus II, P = 0.3488; stage I versus III, P = 0.1613; stage I versus IV, P = 0.0293. Bar denotes median filter radius.
