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

Abstract

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.

Structural and functional properties of SARS-CoV-2 spike protein: potential antivirus drug development for COVID-19

“…Therefore, furin inhibitors can be used as a drug therapy for SARS-CoV-2 [41]. Patent literature since 1994 describes the use of furin or its inhibitors in the treatment of diseases, and some furin inhibitors that have been reported, including α-1-PDX (α1-antitrypsin Portland) [76], hexa-D-arginine(D6R) [77], serpin proteinase inhibitor 8 (PI8) [78], and a peptidomimetic furin inhibitor [79].…”

Hippo signaling in cancer: regulatory mechanisms and therapeutic strategies

“…Overexpression of YAP/TAZ has been found to induce EMT in various tumor cells, [122,123] while knockdown of YAP/TAZ can inhibit EMT. [124,125] Secondly, YAP promotes cell migration and invasion. For example, multiple studies have shown that knockdown or overexpression of LATS1/2 can promote or inhibit the migration and invasion of tumor cells, respectively.…”

Antimicrobial peptides: A plausible approach for COVID-19 treatment

“…It has been reported to suppress the concentration of processed S protein fragments, cytopathic effects, and viral production in SARS-CoV-2-infected VeroE6 cells, indicating furin inhibitor activity [ 67 , 68 ]. D6R, another furin inhibitor, is safer and therapeutically more effective than the other members of this class, but its effectiveness in SARS-CoV-2 infection is yet to be explored [ 69 ]. MI-1851 is another synthetic furin inhibitor that has been reported to suppress SARS-CoV-2 replication in Calu-3 human airway cells, leading to a 30- to 190-fold reduction in virus titers at a dose of 10 μM [ 70 , 71 ].…”