Fig. 5: Jagged2 is functionally regulated by the TGF-β-Smad3 signaling pathway in ovarian cancer omental metastasis.

A Gene-set enrichment analysis (GSEA) of the TGF-β-responsive genes set in a ranked list of differentially expressed genes in primary ovary tumors versus omental metastatic tumor cells (GSE2109; P = 0.037). The bottom panel shows a corresponding heat map of core TGF-β gene sets with elevated expression in two groups. B Jagged2 mRNA expression in response to TGF-β treatment in ovarian cancer cell lines. **P < 0.01, ***P < 0.001. C Jagged2 mRNA expression in SKOV3-ip cells treated with either DMSO or TGF-β-receptor inhibitor (EMD616451) for 24 hours. ***P < 0.001. D Cell proliferation assay of SKOV3-ip cells treated with either DMSO or TGF-β-receptor inhibitor (EMD616451) for the indicated time. *P < 0.05, ***P < 0.001. E Jagged2 mRNA expression in ovarian cancer cells treated with either DMSO or Smad3 inhibitor (SIS3) for 24 hours. ***P < 0.001. F Number of invaded cells in the indicated cells with altered expression of Jagged2 and Smad3. **P < 0.01, ***P < 0.001. G Representative images of the omental region in mice from experimental groups on day 10. (left) Quantification of tumor numbers in each group of experimental mice. Data in the figure represent average +/- SEM, SD. **P < 0.01, ***P < 0.001. H Western blot analysis showing Jagged2, Smad3, and phospho-Smad3 expression in the indicated cells with altered Jagged2 and Smad3. I Western blot analysis of Jagged2, phospho-Smad3, and Smad3 protein levels in the control or Smad3 knockdown in Jag2OE cells with or without stimulation of TGF-β. J Western blot analysis showing Jagged2 protein expression in the control and Jag2KD SKOV3-ip cells with or without TGF-β treatment. Data in the figure represent average and +/-SEM; P-values were determined using the Student’s t-test unless otherwise indicated.