Furin Promotes Epithelial Mesenchymal Transition In Pancreatic Cancer Cells Via Hippo-YAP Pathway

Objective: Furin,as an earliest discovered proprotein convertase,plays a key role in a lot of diseases,and contacts with tumor metastasis.Furin can process a series of notorious molecules which are involved directly or indirectly in tumorigenesis and tumor development and contribute to aggression and metastatic potential of cancer cells.However,the role of Furin targeting pancreatic cancer cells remains to be examined.This study aims at investigating the effects of Furin on the cell proliferation,migration and invasion in pancreatic cancer.Methods: The plasmid sh-Furin and Flag-Furin were designed and constructed to change the expression of Furin for Subsequent experiments.Realtime PCR and Western Blot were used to test the m RNA and protein level of Furin in pancreatic cancer cells.We studied the effects of Furin on proliferation,migration and invasion in pancreatic cancer cells with CCK-8 assays,transwell migration assays and transwell invasion assays.The relavant protein levels of epithelial mesenchymal transition like E-cadherin,N-cadherin,Vimentin and the relavant protein levels of Hippo-YAP pathway such as YAP,p-YAP,Mob1 and p-Mob1 were measured by Western Blot.Results: First,we found that Furin knockdown or Furin inhibitor D6 R remarkably reduced the abilities of proliferation,invasion and migration in Bx PC3 or SW1990 cells,and Furin overexpression promoted the above behaviors in PANC1 and Pa Tu8988 cells.Further evidence revealed that Furin knockdown or Furin inhibitor D6 R led to upregulation of E-cadherin(epithelial marker),and downregulation of N-cadherin and Vimentin(mesenchymal markers)in Bx PC3 and SW1990 cells,whereas Furin overexpression significantly resulted in the opposite effects in PANC1 and Pa Tu8988 cells.Furthermore,our data showed that Furin knockdown,Furin inhibitor D6 R or Furin overexpression significantly affected YAP phosphoration level and total YAP protein level,indicating that Hippo-YAP pathway was involved in the regulation of epithelial mesenchymal transition in pancreatic cancer cells.We found that Furin promoted cell proliferation,migration and invasion and functioned as an oncogene in pancreatic cancer cells.Importantly,Furin promoted epithelial mesenchymal transition and regulated it probably via the Hippo-YAP signal pathway.Conclusion:It is suggested that Furin promoted the abilities of growth,invasion,migration and epithelial mesenchymal transition in pancreatic cancer cells,and regulated it probably via Hippo-YAP pathway.Furin may be a potential target for anti-pancreatic cancer.