4.7 Article

T-LAK cell-originated protein kinase (TOPK): an emerging prognostic biomarker and therapeutic target in osteosarcoma

期刊

MOLECULAR ONCOLOGY
卷 15, 期 12, 页码 3721-3737

出版社

WILEY
DOI: 10.1002/1878-0261.13039

关键词

immunohistochemistry; osteosarcoma; prognostic biomarker; TOPK

类别

资金

  1. Department of Orthopaedic Surgery, David Geffen School of Medicine at UCLA

向作者/读者索取更多资源

The study revealed that high expression of TOPK in osteosarcoma is associated with metastasis, disease status, and shorter overall survival. Silencing TOPK with siRNA or inhibiting it with the selective inhibitor OTS514 can suppress proliferation and migration of osteosarcoma cells, enhance chemotherapeutic sensitivity, and exert synergistic effects with doxorubicin or cisplatin.
T-lymphokine-activated killer (T-LAK) cell-originated protein kinase (TOPK) is an emerging target with critical roles in various cancers; however, its expression and function in osteosarcoma remain unexplored. We evaluated TOPK expression using RNA sequencing and gene expression data from public databases (TARGET-OS, CCLE, GTEx, and GENT2) and immunohistochemistry in an osteosarcoma tissue microarray (TMA). TOPK gene expression was significantly higher in osteosarcoma than normal tissues and directly correlated with shorter overall survival. TOPK was overexpressed in 83.3% of the osteosarcoma specimens within our TMA and all osteosarcoma cell lines, whereas normal osteoblast cells had no aberrant expression. High expression of TOPK associated with metastasis, disease status, and shorter overall survival. Silencing of TOPK with small interfering RNA (siRNA) decreased cell viability, and inhibition with the selective inhibitor OTS514 suppressed osteosarcoma cell proliferation, migration, colony-forming ability, and spheroid growth. Enhanced chemotherapeutic sensitivity and a synergistic effect were also observed with the combination of OTS514 and either doxorubicin or cisplatin in osteosarcoma cell lines. Taken together, our study demonstrated that TOPK is a potential prognostic biomarker and therapeutic target for osteosarcoma treatment.

作者

我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。

评论

主要评分

4.7
评分不足

次要评分

新颖性
-
重要性
-
科学严谨性
-
评价这篇论文

推荐

暂无数据
暂无数据