PREX2 promotes the proliferation, invasion and migration of pancreatic cancer cells by modulating the PI3K signaling pathway

Abstract

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.

Haplotype-resolved and integrated genome analysis of the cancer cell line HepG2

“…The gene overlap between HepG2 PPA and the Sanger Cancer Gene Census is 19 (Supplementary Table S6). HepG2 PPA variants include oncogenes and tumor suppressors such as NRAS (47), STK11/LKB1 (48) and PREX2 (49,50) as well as other genes recently found to play critical roles in driving cancer such as CDK12 (51) and IKBKB (52,53) . RP1L1 , which was recently found to be significantly mutated in hepatocellular carcinoma (45), is also present among the PPA variants.…”

Haplotype-resolved and integrated genome analysis of the cancer cell line HepG2

“…For example, we identified CN changes (CN=3) over the oncogene VEGFA (6p21.1) which is widely known as a key mediator of angiogenesis in cancer (Carmeliet 2005). We see mutations in oncogenes and tumor-suppressor genes in HepG2, such as NRAS (Pylayeva-Gupta et al 2011), STK11/LKB1 (Zhou et al 2014), and PREX2 (Berger et al 2012;Yang et al 2016), as well as in the Wnt-pathway gene CTNNB1 due to the presence of either HepG2-specific protein-altering changes or small-scale structural changes (Table S5, Table S6, Dataset 1, Dataset 4, Supplemental Data). Moreover, we also identified mutations in genes recently found to play critical roles in driving cancer such as CDK12 (Paculová and Kohoutek 2017) and IKBKB (Xia et al 2012;Kai et al 2014).…”

“…The gene overlap between HepG2 PPA and the Sanger Cancer Gene Census is 19 (Table S6). HepG2 PPA variants include oncogenes and tumor suppressors such as NRAS (Pylayeva-Gupta et al 2011), STK11/LKB1 (Zhou et al 2014), and PREX2 (Berger et al 2012;Yang et al 2016) as well as other genes recently found to play critical roles in driving cancer such as CDK12 (Paculová and Kohoutek 2017) and IKBKB (Xia et al 2012;Kai et al 2014). RP1L1, which was recently found to be significantly mutated in hepatocellular carcinoma (Cancer Genome Atlas Research Network 2017) is also present among the PPA variants.…”

Investigation of Aberrantly Methylated Differentially Expressed Genes in Pancreatic Cancer by Integrated Bioinformatics Analysis

“…As we all know, the adhesion function of cells is the primary step for tumor metastasis [46], and the adhesion function enhanced by the focal adhesion and ECM-receptor interaction can accelerate cancer cell metastasis in the blood vessels. The PI3K signaling pathway is activated in a variety of tumors including pancreatic cancer, and the activation of PI3K signaling pathway promotes the metastasis of tumor cells [47].…”