Fig. 4: NALCN loss-of-function increases tumor metastasis.
From: The NALCN channel regulates metastasis and nonmalignant cell dissemination
a, Unsupervised hierarchical clustering of P1KP (GAC, n = 10; lung adenocarcinoma, n = 6; prostatic adenocarcinoma, n = 2), V1KP (IAC, n = 19), Pdx1KP (PAC, n = 13) and P1;PtenFlx/Flx;Trp53Flx/Flx (P1PtP) (hepatobiliary, n = 3; lung adenocarcinoma, n = 1) primary tumors and metastatic (liver, n = 2; peritoneum, n = 11; kidney, n = 1; thoracic cavity, n = 4; lung, n = 1; lymph node, n = 2) tumors. Heatmap reports enrichment of primary tumor transcriptomes in metastatic tumors. b, Exemplar ZSG+ metastatic tumors (met, outlined). Scale bar, 0.5 cm. c, Photomicrographs (H&E (left) and immunohistochemistry/fluorescence(right)) of the metastases in b. Scale bar, 50 μm. All enumerated metastases were evaluated using H&E (full list is given in Supplementary Table 9; n = 7,076 metastases); n = 59 metastases were evaluated by ZSG for IHC and n = 20 metastases were evaluated by immunofluorescence. Single-channel images are shown in Supplementary Fig. 1. d, Left: cumulative total number of adenocarcinoma metastases per mouse post Cre-recombination (two-tailed Mann–Whitney U-test, total tumor burden in Nalcn-deleted versus wild-type mice; Supplementary Table 9). Right: total metastases per mouse in anatomical regions. Male/female (M:F) and P3/P60 mice are shown. V1KP IAC for individual organs: liver, *P = 0.0371 (NalcnFlx/Flx); kidney, *P = 0.0229 (NalcnFlx/Flx); and peritoneum, *P = 0.0492 (Nalcn+/Flx) and **P = 0.0015 (NalcnFlx/Flx). Pdx1KP PAC individual organs: lung, *P = 0.0328 (Nalcn+/Flx); and peritoneum, **P = 0.0050 (Nalcn+/Flx). P1KP GAC and IAC individual organs: lung, **P = 0.0085 (Nalcn+/Flx) and **P = 0.0048 (NalcnFlx/Flx). e, Metastatic burden and organ metastases in V1KP-IAC gadolinium or control treated mice. **P = 0.0090, two-tailed Mann–Whitney U-test.
