title: PREX2 promotes the proliferation, invasion and migration of pancreatic cancer cells by modulating the PI3K signaling pathway.
abstract: Phosphatidylinositol-3,4,5-trisphosphate-dependent Rac exchanger factor 2 (PREX2) is a novel regulator of the small guanosine triphosphatase Rac, and has been observed to be implicated in human cancer by inhibiting the activity of phosphatase and tensin homolog (PTEN), thus upregulating the activity of the phosphoinositide 3-kinase (PI3K) signaling pathway. However, the exact role of PREX2 in pancreatic cancer has not been reported to date. In the present study, the expression levels of PREX2 were observed to be frequently increased in pancreatic cancer specimens compared with those in their matched adjacent normal tissues. In addition, PREX2 expression was also frequently upregulated in several pancreatic cancer cell lines, including AsPC-1, BxPC-3, PANC-1 and CFAPC-1, compared with that in the normal pancreatic epithelial cell line HPC-Y5. Overexpression of PREX2 significantly promoted the proliferation, invasion and migration of pancreatic cancer PANC-1 cells, while small interfering RNA-induced knockdown of PREX2 expression significantly inhibited the proliferation, invasion and migration of these cells. Investigation of the molecular mechanism revealed that the overexpression of PREX2 upregulated the phosphorylation levels of PTEN, indicating that the activity of PTEN was reduced, which further increased the phosphorylation levels of AKT, which indicated that the activity of the PI3K signaling pathway was upregulated. By contrast, knockdown of PREX2 upregulated the activity of PTEN and inhibited the activity of the PI3K signaling pathway. In conclusion, the present study demonstrated that PREX2 regulates the proliferation, invasion and migration of pancreatic cancer cells, probably at least via modulation of the activity of PTEN and the PI3K signaling pathway.
authors.affiliation: Department of General Surgery, Xiangya Hospital of Central South University, Changsha, Hunan 410008, P.R. China.
authors.forename: Jianyi
authors.initials: J
authors.lastname: Yang
authors.affiliation: Department of General Surgery, Xiangya Hospital of Central South University, Changsha, Hunan 410008, P.R. China.
authors.forename: Xuejun
authors.initials: X
authors.lastname: Gong
authors.affiliation: Department of General Surgery, Xiangya Hospital of Central South University, Changsha, Hunan 410008, P.R. China.
authors.forename: Lu
authors.initials: L
authors.lastname: Ouyang
authors.affiliation: Department of General Surgery, Xiangya Hospital of Central South University, Changsha, Hunan 410008, P.R. China.
authors.forename: Wen
authors.initials: W
authors.lastname: He
authors.affiliation: Department of General Surgery, Xiangya Hospital of Central South University, Changsha, Hunan 410008, P.R. China.
authors.forename: Rou
authors.initials: R
authors.lastname: Xiao
authors.affiliation: Department of General Surgery, Xiangya Hospital of Central South University, Changsha, Hunan 410008, P.R. China.
authors.forename: Li
authors.initials: L
authors.lastname: Tan
keywords: invasion; migration; pancreatic cancer; phosphatidylinositol-3,4,5-trisphosphate-dependent Rac exchanger factor 2