Furin inhibitor D6R suppresses epithelial-mesenchymal transition in SW1990 and PaTu8988 cells via the Hippo-YAP signaling pathway.

Abstract

Hexa-D-arginine (D6R), an inhibitor of furin, has potential therapeutic applications in different types of human tumor. However, the function of D6R in targeting pancreatic cancer cells remains to be elucidated. In the present study, the proliferation, invasion and migration abilities of SW1990 and PaTu8988 cells were examined using a Cell Counting Kit-8, and Transwell and wound healing assays. Subsequently, the expression of proteins associated with epithelial-mesenchymal transition (EMT) and the Hippo-yes-associated protein (YAP) pathway were detected using western blot analysis. It was revealed that D6R significantly inhibited the proliferation, migration and invasion abilities of SW1990 and PaTu8988 cells. Additionally, D6R led to the upregulation of E-cadherin (an epithelial marker), and the downregulation of N-cadherin and vimentin (mesenchymal markers) in SW1990 and PaTu8988 cells. Furthermore, the results of the present study revealed that D6R significantly affected the YAP phosphorylation level and the total YAP protein level, indicating that D6R was functionally involved in the Hippo-YAP signaling pathway. It has been suggested that D6R-suppressed EMT in SW1990 and PaTu8988 cells may occur via the Hippo-YAP pathway and that it may be a feasible drug to ameliorate the malignant phenotype of SW1990 and PaTu8988 cells.