PREX2 promotes the proliferation, invasion and migration of pancreatic cancer cells by modulating the PI3K signaling pathway
Authors: Xuejun Gong
Li Tan
Lu Ouyang
Jianyi Yang
Wen He
Rou Xiao
Journal: Oncology Letters (2016)
Discipline: CLINICAL MEDICINE
Keywords: invasion; migration; pancreatic cancer; phosphatidylinositol-3,4,5-trisphosphate-dependent Rac exchanger factor 2.
Affiliations: Department of General Surgery, Xiangya Hospital of Central South University, Changsha, Hunan 410008, P.R. China.

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. 

Retracted: Yes

PubPeer comments:
 Fig 3.  Transwell assay was performed to determine the invasive capacity of PANC-1 cells transfected with pcDNA3.1-PREX2 plasmid or PREX2-specific small interfering RNA. Non-transfected PANC-1 cells were used as control . ![file] For comparison: Fig 3 C D from [Zhang et al (2016)] .  Transwell assay were performed to examine the migratory and invasive capacities of Saos-2 and U2OS cells transfected with miR-205 mimic or miR-negative control (NC) mimic , and Fig 7C D,  Transwell assay were performed to examine cell migration and invasion of MG63 or U2OS cells transfected with miR-205 mimic, or co-transfected with miR-205 mimic and RUNX2 plasmid . ![] (plus numerous other manifestations of the same panels, linked in that thread). , 
 Figure 4.  Wound healing assay was performed to determine the migratory capacity of PANC-1 cells transfected with pcDNA3.1-PREX2 plasmid or PREX2-specific small interfering RNA. As control, non-transfected PANC-1 cells were used . ![file] For comparison, Fig 5A from [Wang et al (2016)] .  Wound healing assay to determine the migratory capacity of U2OS cells transfected with miR-101 mimics or c-FOS siRNA, or co-transfected with miRu2011101 mimics and cu2011FOS plasmid . ![file] Surprisingly many repeated panels. ------------------------------------------------- UPDATE: Green rectangle indicates a panel shared with Fig 3A of [Jiang et al (2016)] .  Cell migration assay was performed to determine cell invasion levels in ccRCC cells treated with Aza (10 nM) for 72 h . ![file] , 
 Retracted [12 July 2021] . -------------------------------- Following the publication of this paper, it was drawn to the Editorsu2019 attention by a concerned reader that certain of the Transwell cell migration data shown in Fig. 3, and the scratch-wound assay data in Fig. 4, were strikingly similar to data appearing in different form in other articles by different authors. Owing to the fact that the contentious data in the above article had already been published elsewhere, or were already under consideration for publication, prior to its submission to *Oncology Letters*, the Editor has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive any reply. The Editor apologizes to the readership for any inconvenience caused. ,