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

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 dat...

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Autores principales:	Pichaya Thanindratarn, Ran Wei, Dylan C. Dean, Arun Singh, Noah Federman, Scott D. Nelson, Francis J. Hornicek, Zhenfeng Duan
Formato:	article
Lenguaje:	EN
Publicado:	Wiley 2021
Materias:	immunohistochemistry osteosarcoma prognostic biomarker TOPK Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/dad7f96840d24a35ade73793916c2808
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spelling	oai:doaj.org-article:dad7f96840d24a35ade73793916c28082021-12-02T10:31:06ZT‐LAK cell‐originated protein kinase (TOPK): an emerging prognostic biomarker and therapeutic target in osteosarcoma1878-02611574-789110.1002/1878-0261.13039https://doaj.org/article/dad7f96840d24a35ade73793916c28082021-12-01T00:00:00Zhttps://doi.org/10.1002/1878-0261.13039https://doaj.org/toc/1574-7891https://doaj.org/toc/1878-0261T‐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.Pichaya ThanindratarnRan WeiDylan C. DeanArun SinghNoah FedermanScott D. NelsonFrancis J. HornicekZhenfeng DuanWileyarticleimmunohistochemistryosteosarcomaprognostic biomarkerTOPKNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENMolecular Oncology, Vol 15, Iss 12, Pp 3721-3737 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	immunohistochemistry osteosarcoma prognostic biomarker TOPK Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	immunohistochemistry osteosarcoma prognostic biomarker TOPK Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Pichaya Thanindratarn Ran Wei Dylan C. Dean Arun Singh Noah Federman Scott D. Nelson Francis J. Hornicek Zhenfeng Duan T‐LAK cell‐originated protein kinase (TOPK): an emerging prognostic biomarker and therapeutic target in osteosarcoma
description	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.
format	article
author	Pichaya Thanindratarn Ran Wei Dylan C. Dean Arun Singh Noah Federman Scott D. Nelson Francis J. Hornicek Zhenfeng Duan
author_facet	Pichaya Thanindratarn Ran Wei Dylan C. Dean Arun Singh Noah Federman Scott D. Nelson Francis J. Hornicek Zhenfeng Duan
author_sort	Pichaya Thanindratarn
title	T‐LAK cell‐originated protein kinase (TOPK): an emerging prognostic biomarker and therapeutic target in osteosarcoma
title_short	T‐LAK cell‐originated protein kinase (TOPK): an emerging prognostic biomarker and therapeutic target in osteosarcoma
title_full	T‐LAK cell‐originated protein kinase (TOPK): an emerging prognostic biomarker and therapeutic target in osteosarcoma
title_fullStr	T‐LAK cell‐originated protein kinase (TOPK): an emerging prognostic biomarker and therapeutic target in osteosarcoma
title_full_unstemmed	T‐LAK cell‐originated protein kinase (TOPK): an emerging prognostic biomarker and therapeutic target in osteosarcoma
title_sort	t‐lak cell‐originated protein kinase (topk): an emerging prognostic biomarker and therapeutic target in osteosarcoma
publisher	Wiley
publishDate	2021
url	https://doaj.org/article/dad7f96840d24a35ade73793916c2808
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T‐LAK cell‐originated protein kinase (TOPK): an emerging prognostic biomarker and therapeutic target in osteosarcoma

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