SRPK1 promotes metastasis of esophageal squamous cell carcinoma by phosphorylation of Gli3S664

Abstract Esophageal squamous cell carcinoma (ESCC) is among the most malignant types of digestive malignant tumor. Metastasis and recurrence contribute poor prognosis of ESCC. However, the mechanism of ESCC metastasis remains unclear. Here, we found high levels of Gli3 and p-Gli3S664 in ESCC tissues, which contributed to promote metastasis of ESCC cells in vitro. Importantly, we verified that serine-arginine protein kinase 1 (SRPK1) bound to Gli3 and phosphorylated Gli3 at the ser 664 residue, which promoted migration, invasion, and EMT of ESCC cells. Additionally, we found that dihydroartemisinin (DHA) inhibited metastasis of ESCC cells by downregulating SRPK1-mediated phosphorylation of Gli3S664 in vitro and in vivo. Thus, our findings demonstrate that the SRPK1-p-Gli3S664 axis plays an important role in ESCC metastasis and DHA may be a candidate drug to prevent ESCC metastasis by targeting the SRPK1-p-Gli3S664 axis.