ARHGEF39 promotes gastric cancer cell proliferation and migration via Akt signaling pathway

Abstract

Dbl-family guanine nucleotide exchange factors (GEFs) can activate RhoGTPases by facilitating the exchange of GDP for GTP, the aberrant expression of which has been implicated in tumorigenicity and metastasis of human cancers. ARHGEF39, as a member of Dbl-family GEFs, was reported to be a potential oncogene in human hepatocellular carcinoma previously. However, the role of ARHGEF39 in gastric cancer (GC) remains unclear so far. In the current study, we demonstrated that ARHGEF39 expression was significantly upregulated in GC tissues compared with paired adjacent normal tissues by quantitative real-time PCR analysis. Functional analyses revealed that ARHGEF39 overexpression could promote proliferation, colony formation, and migration of GC cells in vitro, whereas ARHGEF39 knockdown markedly suppressed these phenotypes. Moreover, ARHGEF39 enhanced tumorigenicity and lung metastasis potential of GC cells in nude mice model. Mechanistically, we found that overexpressed ARHGEF39 significantly increased the phosphorylation level of Akt (p-Akt), and its effect on cell proliferation was attenuated by PI3K inhibitor LY294002. Thus, our findings suggest that ARHGEF39 may contribute to cell proliferation and migration in GC via a possible mechanism involving Akt signaling.

Keywords: ARHGEF39; Akt; Cell proliferation; Gastric cancer; Migration.