T‐LAK cell‐originated protein kinase (TOPK): an emerging prognostic biomarker and therapeutic target in osteosarcoma
| Autor: | Francis J. Hornicek, Ran Wei, Noah Federman, Pichaya Thanindratarn, Dylan C. Dean, Arun S. Singh, Scott D. Nelson, Zhenfeng Duan |
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| Rok vydání: | 2021 |
| Předmět: |
musculoskeletal diseases
0301 basic medicine Cancer Research Small interfering RNA TOPK Bone Neoplasms Biology 03 medical and health sciences 0302 clinical medicine Cell Line Tumor osteosarcoma Gene expression Genetics medicine Humans Gene silencing Viability assay Killer Cells Lymphokine-Activated prognostic biomarker neoplasms Research Articles RC254-282 Mitogen-Activated Protein Kinase Kinases Tissue microarray Lymphokine-activated killer cell Cell growth Neoplasms. Tumors. Oncology. Including cancer and carcinogens General Medicine Prognosis medicine.disease 030104 developmental biology Oncology 030220 oncology & carcinogenesis immunohistochemistry Cancer research Molecular Medicine Osteosarcoma Biomarkers Research Article |
| Zdroj: | Molecular Oncology, Vol 15, Iss 12, Pp 3721-3737 (2021) Molecular Oncology |
| ISSN: | 1878-0261 1574-7891 |
| DOI: | 10.1002/1878-0261.13039 |
| Popis: | 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. TOPK is aberrantly expressed in osteosarcoma and significantly correlates with shorter overall survival (OS). Therapeutic inhibition of TOPK decreases osteosarcoma cell growth, proliferation, migration, and colony formation. These findings indicate TOPK as a prognostic biomarker for OS and a potential therapeutic target in patients with osteosarcoma. |
| Databáze: | OpenAIRE |
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