GINS2 promotes EMT in pancreatic cancer via specifically stimulating ERK/MAPK signaling
Authors: Longping Huang
Dawei Ji
Haijun Fan
Chuanping Chen
Si Chen
Weiwei Sheng
Journal: Cancer Gene Therapy (2020)
Discipline: CLINICAL MEDICINE
Keywords: GINS2; oncogene; pancreatic cancer; epithelial-mesenchymal-transition (EMT); tumor size
Affiliations: Department of General Surgery, Hepatobiliary Surgery, The Fourth People's Hospital of Shenyang, Shenyang, 110031, China., Department of Anesthesiology, The Fourth People's Hospital of Shenyang, Shenyang, 110031, China., Department of General Surgery, The Fourth People's Hospital of Shenyang, Shenyang, 110031, China., Department of Clinical Laboratory, The Sixth Peoples' Hospital of Shenyang, Shenyang, 110003, Liaoning, China., Department of Gastrointestinal Surgery, The First Hospital, China Medical University, Shenyang, 110001, China. .

Abstract:  Go-Ichi-Ni-San 2 (GINS2), as a newly discovered oncogene, is overexpressed in several cancers. However, the specific role of GINS2 in the development of pancreatic cancer (PC), to our knowledge, is poorly understood. We systematically explored the potential role of GINS2 in epithelial-mesenchymal-transition (EMT)-stimulated PC in vitro and vivo. GINS2 was overexpressed in human PC specimens, which was positively associated with tumor size (P = 0.010), T stage (P = 0.006), vascular invasion (P = 0.037), and the poor prognosis (P = 0.004). Interestingly, a close correlation between GINS2, E-cadherin, and Vimentin (P = 0.014) was found in human PC specimens and cell lines that coordinately promoted the worse survival of PC patients (P = 0.009). GINS2 overexpression stimulated EMT in vitro, including promoting EMT-like cellular morphology, enhancing cell motility, and activating EMT and ERK/MAPK signal pathways. However, PD98059, a specific MEK1 inhibitor, reversed GINS2 overexpression-stimulated EMT in vitro. Conversely, GINS2 silencing inhibited EMT in PANC-1 cells, which was also rescued by GINS2-GFP. Moreover, GINS2 was colocalized and co-immunoprecipitated with ERK in GINS2 high-expression Miapaca-2 and PANC-1 cells, implying a tight interaction of GINS2 with ERK/MAPK signaling. Meanwhile, GINS2 overexpression inhibited distant liver metastases in vivo, following a tight association with EMT and ERK/MAPK signaling, which was reversed by MEK inhibitor. Overexpression of GINS2 contributes to advanced clinical stage of PC patient and promotes EMT in vitro and vivo via specifically activating ERK/MAPK signal pathway. 

Retracted: No

PubPeer comments:
 The micrographs of HE staining in Figure 8 look unusual. The many white circles are identical. Why? ![file] , 
 The white dots look as if someone was trying to delineate a section of the image for image-analysis purposes. , 
 #2 Thanks for your nice attention to our MS. As you mentioned, the white dots were marked by ourselves to distinguish the border between normal liver tissues and liver metastasis. HE staining just showed a general area of liver metastasis in each group. These images with 100x magnification are hardly to reflect the whole liver metastasis area in each group. Thus, no any of image-analysis were used in the HE staining in current study. We just only compared liver metastasis numbers in each group in Figure 8B. Please check the data once again. If you have any questions, please don t hesitate to contact us. Thank you so much. , 
 #1 Thanks for your nice attention to our MS. All the identical white dots were marked by ourselves to distinguish the border between normal liver tissues and liver metastasis. HE staining just showed a general area of liver metastasis in each group marked with white dots without any image-analysis and statistic data here. If you have any questions, please don t hesitate to contact us. Thank you so much. #1 #1 #3 ,