Furin promotes epithelial-mesenchymal transition in pancreatic cancer cells via Hippo-YAP pathway

弗林蛋白酶通过 Hippo-YAP 通路促进胰腺癌细胞上皮-间质转化

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作者:Youli Zhang, Meng Zhou, Hong Wei, Hailang Zhou, Junbo He, Ying Lu, Dawei Wang, Baoding Chen, Jian Zeng, Wanxin Peng, Fengyi Du, Aihua Gong, Min Xu

Abstract

Furin, a well-characterized proprotein convertase, plays an important role in many diseases and links to tumor metastasis. However, the role of furin in pancreatic cancer progression remains to be elucidated. In the present study, we found that furin promotes the growth and the epithelial-mesenchymal transition (EMT) of pancreatic cancer cells. First, we found that furin knockdown significantly inhibited proliferation, invasion and migration in BxPC3 and SW1990 cells, while furin overexpression promoted the above behavior in PANC1 and PaTu8988 cells. Further evidence revealed that furin knockdown resulted in the upregulation of E-cadherin (epithelial marker), and the downregulation of N-cadherin and Vimentin (mesenchymal markers) in BxPC3 and SW1990 cells, whereas furin overexpression remarkably led to the opposite effects in PANC1 and PaTu8988 cells. Furthermore, our data showed that Furin knockdown, furin inhibitor D6R or overexpression significantly affected YAP phosphoration level and total YAP protein level, indicating that furin was involved in Hippo-YAP pathway. It is suggested that furin promotes epithelial-mesenchymal transition in pancreatic cancer cells probably via Hippo-YAP pathway and may be a potential target for anti-pancreatic cancer.

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