LAUSR

Background The poor prognosis of patients with pancreatic ductal adenocarcinoma (PDAC) is partially attributed to the invasive and metastatic behavior of this disease. Epithelial cell transforming 2 (ECT2) is a guanine nucleotide exchange factor (GEF) of the Rho family of GTPases. It has also been reported that upregulation of ECT2 in pancreatic cancer, but the role and mechanism of ECT2 have not been previously determined. Methods Expression of ECT2 in PDAC and PDAC cell lines was characterized using immunohistochemistry and Western blotting. ECT2 was overexpressed via retroviral transduction and knocked down in PDAC cells using shRNA. Cell proliferation was determined using a colorimetric cell viability assay, and cell migration and invasion using transwells. Expression of markers of epithelial-mesenchyme transition (EMT) was assayed by Western blotting. ECT2 and cell division cycle 42 (Cdc42) were interrogated by immunoprecipitation and Western blot. The functional role of Cdc42 was determined using siRNA. Results We found ECT2 was significantly upregulated in PDAC tissues and cells, correlated with more advanced clinicopathological features. ECT2 regulated invasion and migration of PDAC cells in vitro and in vivo. ECT2 silencing downregulated EGFR expression via accelerating EGFR degradation in pancreatic cancer cells. Immunoprecipitation assay further confirmed that ECT2 interacted with Cdc42. More importantly, ECT2 silence markedly decreases Cdc42 activity. The promoting effect of ECT2 on migration can be decreased by the siRNA against Cdc42. Conclusions Overall, this study shows that ECT2 increases EGFR and promotes tumorigenicity of pancreatic cancer cells by enhancing Cdc42 activity.