Expression and clinical significance of threonine and tyrosine protein kinase (TTK) in osteosarcoma

Zhe Dong, Ke Sun, Yanjun Luan, Yun Chen, Wei Wang, Dongqian Liu, Chao Cheng, Fujun Xiong, Yong Xi


Background: The purpose of the present study was to detect the expression level of threonine and tyrosine protein kinase (TTK) in osteosarcoma (OS) and investigate whether TTK could be a biomarker for early diagnosis or even a molecular targeted therapy for OS.
Methods: First, by using GEO dataset we analyzed the expression level of TTK in sarcoma. Then, by using immunohistochemistry (IHC) we investigated the TTK expression in tissue microarrays (TMAs) to verify the results. Next, we suppressed TTK expression in MG-63 and U2-OS cell lines, protein expression were analyzed by Western blot respectively as well as cell viability and migration were evaluated by Cell Counting Kit-8 (CCK-8) and transwell chamber assay. Finally, proteins that are associated with MAPK signal pathway were detected by Western blot.
Results: GEO dataset revealed that TTK expression in normal bone tissue was significantly lower than that in sarcoma. And the result of IHC verified the higher expression of TTK in OS. In MG-63/siTTK and U2-OS/siTTK cells, the expression levels of TTK down-regulated significantly and the proliferation and migration were decreased with apoptosis increased compared to MG-63 and U2-OS cells. Additionally, MAPK signal pathway related protein expressions were reduced obviously.
Conclusions: TTK expression in OS tissue was significantly higher than in normal tissue, it may provide additional help for the early diagnosis or even therapeutic target of OS. In addition, the internal mechanism still needs further investigation.