FV-429 suppresses cancer cell migration and invasion by EMT via the Hippo/YAP1 pathway in pancreatic cancer cells

Abstract

Pancreatic cancer is one of the most common malignant tumors of the digestive system, with the majority of patients not succumbing to the primary tumor but rather to metastasis. Epithelial-mesenchymal transition (EMT) is abnormally activated in numerous cancers, whereby it promotes tumor cell migration and invasion. Yes-associated protein 1 (YAP1) is commonly overexpressed in various cancer types and plays an oncogenic role. We demonstrated that FV-429, a derivative of the natural flavonoid wogonin, inhibited the invasion and metastasis of pancreatic cancer cells by modulating EMT-related proteins. FV-429 enhances the expression of p-LATS1, thereby promoting the conversion of YAP1 to p-YAP1. Meanwhile, it suppresses the nuclear translocation of YAP1, thereby affecting the expression of E-cadherin and snail1, which, in turn, impacts the EMT. The Hippo-signaling pathway inhibitor TDI-011536 was used to validate these results. In vivo , a mouse model of pancreatic cancer lung metastasis was established using PANC02 cells to validate the antimetastatic effect of FV-429, which confirmed its action through the Hippo/YAP1 pathway. In addition, FV-429 demonstrated high safety and low toxicity. In conclusion, we demonstrated that FV-429 inhibits migration, invasion, and metastasis of human pancreatic cancer cells by affecting the Hippo/YAP1 pathway, suggesting that FV-429 has the potential to be a novel therapeutic agent for pancreatic cancer.

Keywords: EMT; FV-429; Hippo pathway; metastasis; pancreatic cancer.