Dysregulation of the FGF/FGFR signaling pathway within the fibroblast growth factor receptor (FGFR) family is closely associated with tumorigenesis, progression, and resistance to anticancer drugs. Fibroblast growth factor receptor 3 (FGFR3) is a member of this family. Here, researchers investigated the effects of FGFR3 knockdown on the biological behavior of intrahepatic cholangiocarcinoma (ICC) cells. Their study found that FGFR3 knockdown inhibited ICC cell migration, invasion, and proliferation through scratch assays, Transwell migration and invasion assays, and cell proliferation assays. FGFR3 knockdown significantly downregulated the protein expression levels of MMP2, cyclin D1, and N-cadherin, but had no significant effect on the protein expression levels of MMP9, cyclin D3, vimentin, and E-cadherin. Furthermore, bioinformatics analysis and Western blotting experiments confirmed that ERK/c-Myc may be its signaling pathway. In conclusion, FGFR3 knockdown inhibits the migration, invasion, and proliferation of ICC cells. This suggests that FGFR3 may be a therapeutic target for ICC and could potentially improve the cure rate for patients with intrahepatic cholangiocarcinoma who receive FGFR inhibitor therapy.
To investigate whether FGFR3 expression affects the migration and invasion abilities of RBE cells, researchers conducted scratch wound healing, Transwell migration, and Transwell invasion assays. The scratch wound healing assay showed that FGFR3-knockdown RBE cells had significantly lower migration ability than the negative control group (Figures 1A and 1B). The Transwell migration assay showed similar results (Figures 1C and 1D). Furthermore, the Transwell invasion assay showed that FGFR3-knockdown RBE cells had significantly lower invasive ability than control cells (Figures 1C and 1E). Subsequently, researchers analyzed MMP expression levels using Western blotting. The results showed that, compared to the control group, MMP2 expression was significantly downregulated in FGFR3-knockdown cells, while MMP9 expression remained largely unchanged.
Figure 1. Knockdown expression of FGFR3 suppressed ICC cell migration and invasion. (Chen Y, et al., 2023)