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T‐LAK cell‐originated protein kinase (TOPK): an emerging prognostic biomarker and therapeutic target in osteosarcoma
- Source :
- Molecular Oncology, Vol 15, Iss 12, Pp 3721-3737 (2021), Molecular Oncology
- Publication Year :
- 2021
- Publisher :
- Wiley, 2021.
-
Abstract
- 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.<br />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.
- Subjects :
- 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
Subjects
Details
- ISSN :
- 18780261 and 15747891
- Volume :
- 15
- Database :
- OpenAIRE
- Journal :
- Molecular Oncology
- Accession number :
- edsair.doi.dedup.....75647682d0b21b2d5d95553b6dc4c200