SRPX2 Promotes Cell Proliferation and Invasion in Osteosarcoma Through Regulating Hippo Signaling Pathway

Background/Purpose: Osteosarcoma (OS), a primary bone malignancy, is characterized by a high rate of metastasis. It has been found that Sushi repeat containing protein X-linked 2 (SRPX2) is involved in tumor cell proliferation, adhesion, invasion and migration. The current work aimed to explore the effect of SRPX2 on OS cell invasion and proliferation. Methods: Immunohistochemistry (IHC), Western blotting and reverse transcriptionpolymerase chain reaction (RT-PCR) were used to detect the expression of the associated protein in OS tissues and cell lines. Cell counting kit-8 (CCK8), transwell and colony formation assays were used to determine cell viability, invasion, and proliferation, respectively. The in vivo tumorigenic ability of SRPX2 gene was determined using nude mouse tumorigenesis test. Results: SRPX2 knockdown suppressed the viability, while SRPX2 overexpression increased the invasion and colony formation ability of the cells in vitro. In vivo experiments demonstrated that SRPX2 knockdown inhibited tumor growth and invasion as evidenced by decreased Ki67 and N-cadherin levels, and increased E-cadherin level. Downregulation of SRPX2 increased YAP phosphorylation resulting in reduced nuclear translocation to activate Hippo signaling pathway. The promotion of cell viability, colony-forming ability, and invasion, and the inhibition of CTGF, Cyr61, and Birc5 levels promoted by SRPX2 overexpression were reversed by YAP inhibition. Conclusion: SRPX2 increased cell proliferation and invasion in osteosarcoma by activating Hippo signaling pathway.