The crucial role of SRPK1 in IGF-1-induced EMT of human gastric cancer

In recent years, the insulin-like growth factor (IGF-1) and serine-arginine protein kinase 1 (SRPK1) have been reported to be implicated in the pithelial-mesenchymal transition (EMT) in many kinds of malignancies. However, the potential roles of IGF-1-SRPK1 signaling in the EMT of gastric cancer (GC) have not been investigated. In the present study, the in-vitro assays were used to investigate the molecular role of SRPK1 in cell cycle, motility and invasiveness. We demonstrated that the expressions of SRPK1 or insulin-like growth factor receptor 1 (IGF1R) were significantly increased in GC tissues and cells than those in normal tissues and GES-1 cells, and closely associated with metastasis, stage and prognosis. Western blot analysis showed that IGF-1 treatment can induce the expression of p-AKT and EMT biomarkers (N-cadherin, MMP2 and Slug) in a dose-dependent fashion in MGC803 and BGC823 cells. On the other hand, the knockdown of SRPK1 attenuated IGF-1-induced increase of EMT biomarkers and p-AKT. Besides, in-vitro analysis showed that knockdown of SRPK1 induced cell cycle arrest in G0/G1 phase, and affected cell migration and invasion. In conclusion, IGF-1-IGF1R pathway induced the expression of SRPK1 to control the progression of EMT via AKT pathway in the development of GC. Our findings lay a promising foundation for the IGF-1-IGF1R axis-targeting therapy in GC patients.