FGD5 (faciogenital dysplasia-5), a Rho-family guanine nucleotide exchange factor, has been identified as a key regulator of endothelial cells angiogenesis and apoptosis. However, the expression and role of FGD5 in the pathogenesis of gastric cancer remain unknown. In the present study, we first detected FGD5 expression in tumor tissues of different stages by immunofluorescence and confirmed that FGD5 expression was associated with stages in human gastric cancer. Knockdown FGD5 by shRNA in 7901 and BGC823 human gastric cells lines inhibited tumorigenesis and migration in vivo and in vitro. Mechanistically, co-immunoprecipitation (Co-IP) assay showed that FGD5 interacted with EGFR and decreased EGFR ubiquitination. Additionally, FGD5 sustained the activation of EGFR downstream signaling molecules, including STAT3 and pSTAT3. Furthermore, we showed that FGD5 could induce resistance to chemotherapy 5Fu/CIS, however, a well-known STAT3 inhibitor FLL32 could reverse FGD5-induced chemotherapy resistance in vivo. In conclusion, we are the first to demonstrate that FGD5 expression was associated with tumor stage and proliferation in gastric cancer and targeting FGD5 might be a potential therapeutic target for EGFR-STAT3 resistance gastric cancer.
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