The Rho GTPase RhoE exerts tumor-suppressing effects in human esophageal squamous cell carcinoma via negatively regulating epidermal growth factor receptor

Objectives: The objective of this study was to investigate the expression pattern, functions, and possible mechanisms of RhoE/Rnd3, a novel member of the Rho GTPases family, in human esophageal squamous cell carcinoma (ESCC) cells by using molecular and cell-based experiments. Materials and Methods: Quantitative polymerase chain reaction and Western blotting were carried out to determine the mRNA and protein expression of RhoE in ESCC cell lines, respectively. Both 3-(4,5-dimethylthiazol-2-yl)-2,5diphenyltetrazoliumbromide (MTT) and flow cytometry were applied to evaluate the effects of RhoE overexpression on ESCC cell growth and apoptosis. Furthermore, Western blotting was used to test the expression of epidermal growth factor receptor (EGFR) and phosphorylated-extracellular signal-regulated kinase (p-ERK) in ESCC cells after RhoE was forced and expressed. Results: RhoE was downregulated in human ESCC tissues. Overexpression of RhoE inhibited cell growth as assessed by MTT assay and induced apoptosis. Importantly, we proved that RhoE could negatively regulate the protein expression of EGFR and p-ERK, suggesting that RhoE might inhibit ESCC progression through the EGFR/ERK pathway. Conclusion: Our data supported that RhoE could inhibit cell proliferation and promote apoptosis. Moreover, these tumor-suppressing effects might be acted through the negative regulation of EGFR/ERK signaling.