Fig. 7: Targeting BRG1-mediated HLF loss suppresses metastasis across multiple cancer types.

a Workflow for the generation of PDX cell lines, projection plot showing HLF mRNA level and 3D spheroid invasion capability. XP (xenograft patient), the number indicates patient ID. Created in BioRender. Zhou, J. (2025) https://BioRender.com/x5scj3g. b Schematic of kidney orthotopic implantation, representative images of primary tumors (PT) and lung metastatic tumors (Lung-met), and ex vivo signals of Lung-Met relative to its matching PT, n = 7 mice. Created in BioRender. Zhou, J. (2025) https://BioRender.com/x5scj3g. c Representative images and quantification of 3D spheroid invasion in XP374 cells overexpressed with HLF or XP258 cells with HLF knockout. N = 5 (XP374) or n = 3 (XP258) independent cell cultures. Scale bar, 200 µm. d Representative images of primary tumors (PT) and lung metastatic tumors (Lung-met), and ex vivo signals of Lung-Met relative to matched PTs from XP258 cells after orthotopic injection (n = 9, sgCtrl; n = 8, sgHLF). e Representative images and quantification of transwell invasion assay in A375-MA2 cells with HLF overexpression, n = 6 independent cell cultures, Scale bar, 100 µm. f Representative images and quantification of 3D spheroid invasion in cell lines overexpressed with HLF after 2 days (143B, n = 6), 3 days (HCT116, n = 5) and 4 days (H1299, n = 4) of collagen culturing from independent cell cultures. Scale bar, 200 µm. g Schematic of subcutaneous implantation, quantification of luminescence signal in lungs by ex vivo imaging in HCT116 cells (n = 7 mice), and relative quantification of luminescence signal in lungs by ex vivo imaging to primary tumor weight in the H1299 cells (n = 5, Ctrl_EV; n = 6, HLF) overexpressed with HLF followed by subcutaneous implantation in NSG mice. Created in BioRender. Zhou, J. (2025) https://BioRender.com/x5scj3g. h The mRNA levels of SMARCA4 in primary versus metastatic tumors across the indicated cancers. i Representative images and quantification of transwell invasion and 3D collagen invasion in the indicated cell lines treated with AU-15330 for 24 ~ 48 h, n = 5 or 6 independent cell cultures. Transwell invasion, 100 µm, collagen invasion, 200 µm. j Representative images and quantification of 3D collagen invasion in Caki-1 cells with HLF knockout and treatment with 1 µM AU-15330 for 48 h, n = 5 or 6 independent cell cultures. Scale bar, 200 µm. Data are mean (a, fill color shows HLF level, size shows invasion ability), box plots show the median and interquartile range, and whiskers show the data range. Unpaired two-tailed t-test (b–g), Dunn’s test following Kruskal–Wallis test (h) or One-way ANOVA followed by a post hoc Dunnett-t-test (i, j). Source data are provided as a Source Data file.