Fig. 7

DSC1 promotes tumor growth and liver metastasis of colon cancer cells. A The indicated cell lines were transfected with control or DSC1-targeting siRNAs. The transfectants were inoculated subcutaneously. After 6 days, tumors were retrieved and measured. Tumor growth was significantly inhibited after DSC1 knock down (*, p < 0.05). B The same transfectants were inoculated in the spleen of nude mice, which were euthanized after 96 h. RNA from livers were isolated and subjected to RT-PCR to detect human GAPDH. As control, mouse β-actin was also amplified. C Kaplan–Meier survival of mice inoculated in the spleen with control or DSC1-silenced HCT-116 cells. Survival time was significantly enhanced in mice inoculated with DSC1-silenced cells (***, p < 0.001). D CDH17 structure showing the location of the NLV motif. E The indicated cell lysates were subjected to immunoprecipitation using control or anti-CDH17 antibodies in the presence or absence of the CDH17-NLV peptide (10 μg/mL). Immunoprecipitates were analyzed by Western blot to detect DSC1 and CDH17. F, G The indicated cell lines were subjected to migration F or invasion G assays in presence of increasing concentrations of the CDH17-NLV peptide. Migratory speed or number or invasive cells were significantly increased (**, p < 0.05; ***, p < 0.001) or reduced (◊, p < 0.05; ◊◊◊, p < 0.001) after treatment with the peptide. Data are representative of three independent experiments. H SW620 and HCT-116 were exposed to the CDH17-NLV peptide (10 μg/mL) and inoculated in the spleen of nude mice. Liver colonization was assessed as in E. I Functional model of the CDH17/DSC1 complex in colon cancer cells. In mesenchymal cells, the CDH17/DSC1 complex recruits p120-1 into the cell membrane, promoting actin polymerization, cell migration, invasion, and leading to an increase of the metastatic capacity of the colon cancer cells