OncoTargets and Therapy (Dec 2019)
TMEFF2 inhibits pancreatic cancer cells proliferation, migration, and invasion by suppressing phosphorylation of the MAPK signaling pathway
Abstract
Hongchao Han,*,1,2 Zhilin Zhan,*,3 Jie Xu,2 Zhenshun Song1 1Department of Hepatobiliary and Pancreatic Surgery, The Affiliated Shanghai No. 10 People’s Hospital, Nanjing Medical University, Nanjing, People’s Republic of China; 2Department of General Surgery, Yancheng Third People’s Hospital, Yancheng, People’s Republic of China; 3Department of Hepatobiliary Surgery, Chizhou People’s Hospital, Chizhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Zhenshun SongDepartment of Hepatobiliary and Pancreatic Surgery, The Affiliated Shanghai No. 10 People’s Hospital, Nanjing Medical University, No. 301 Yanchang Middle Road, Shanghai 200072, People’s Republic of ChinaTel +86 137 6120 5962Email [email protected]: This paper studied the effect of TMEFF2 expression on pancreatic cancer and its mechanism.Methods: A total of 72 pancreatic cancer patients were enrolled. AsPC1 and Panc1 cells were transfected. SB203580 was used to treat AsPC1 cells. CCK8 assay, colony formation analysis, Transwell experiment and Tunel test were performed. In vivo studies in nude mice were conducted. Immunohistochemistry, qRT-PCR and Western blot were used to detect genes expression.Results: TMEFF2 was downregulated in pancreatic cancer tissues and cells (P<0.001). Low TMEFF2 expression was associated with larger tumor size and advanced stage and poor differentiation (P<0.01). Compared with the NC group, AsPC1 and Panc1 cells of the TMEFF2 group exhibited much lower OD450 values, colony number, tumor volume and weight, migration and invasion cell numbers, obviously higher E-cadherin protein expression, lower Snail, Vimentin, MMP-2 and MMP-9 proteins expression, lower phosphorylation level of MAPK signaling pathway, and more apoptotic cells. AsPC1 cells of the SB203580 group showed much lower OD450 value when compared with the siTMEFF2 group. Significantly decreased colony number, migration and invasion number, higher E-cadherin protein expression and lower Snail, Vimentin, MMP-2 and MMP-9 proteins expression were found in AsPC1 cells of the siTMEFF2+ SB203580 group when compared with the siTMEFF2+ DMSO group.Conclusion: TMEFF2 inhibits pancreatic cancer cells proliferation, migration, and invasion by suppressing the phosphorylation of the MAPK signaling pathway.Keywords: pancreatic cancer, TMEFF2, MAPK signaling, proliferation, migration
