TPX2 Promotes the Proliferation and Metastasis of Osteosarcoma Cells Through Stabilizing E2F1

Abstract

Background: Osteosarcoma (OS) is the most common malignant bone cancer. Recently, more studies have shown that TPX2, a potential oncogene considered to be an important prognostic biomarker, is widely expressed in various tumors. However, until now, little is known about the impacts of TPX2 on the pathogenesis of OS.Methods: TPX2 expression of in OS cells and tissues was detected by Western blot and immunohistochemical analyses. Various assays were used to analyze OS cell proliferation and metastasis in vitro and in vivo. The effect of TPX2 on the expression of E2F1 and proteins encoded by E2F1-regulated genes was evaluated by Western blotting. Coimmunoprecipitation, immunofluorescence and in vitro ubiquitination assays were employed to explore the molecular mechanisms underlying the effect of TPX2 on stabilizing E2F1 and maintaining E2F1 signaling.Results: TPX2 is overexpressed in OS and is significantly correlated with the malignant progression of OS. TPX2 probably plays a critical role in the proliferation and metastasis of OS cells in vitro. Furthermore, TPX2 regulates E2F1 signaling by affecting the stability of E2F1, thereby affecting the proliferation and metastasis of OS cells. In addition, PSMD14 impacts the degradation and regulates the stability of E2F1. Most importantly, TPX2 regulates the interaction of E2F1 and PSMD14 to influence E2F1 degradation.Conclusions: Our research not only identifies TPX2 as a promising therapeutic target in cancer but also illuminates its underlying molecular mechanism. We showed that TPX2 promotes the malignant progression of OS by regulating E2F1 signaling.