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Updated: Nov 2, 2025

Intratibial Osteosarcoma Cell Injection to Generate Orthotopic Osteosarcoma and Lung Metastasis Mouse Models
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T-LAK cell-originated protein kinase (TOPK): an emerging prognostic biomarker and therapeutic target in osteosarcoma

Pichaya Thanindratarn1,2, Ran Wei1,3, Dylan C Dean1

  • 1Department of Orthopaedic Surgery, Sarcoma Biology Laboratory, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.

Molecular Oncology
|June 11, 2021
PubMed

Insights

T-lymphokine-activated killer (T-LAK) cell-originated protein kinase (TOPK) is highly expressed in osteosarcoma, correlating with poor survival. Inhibiting TOPK shows promise for treating osteosarcoma.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • T-lymphokine-activated killer (T-LAK) cell-originated protein kinase (TOPK) is implicated in various cancers.
  • TOPK's role in osteosarcoma has not been previously investigated.

Purpose of the Study:

  • To investigate the expression and function of TOPK in osteosarcoma.
  • To assess TOPK as a potential prognostic biomarker and therapeutic target for osteosarcoma.

Main Methods:

  • Utilized RNA sequencing and public gene expression databases (TARGET-OS, CCLE, GTEx, GENT2).
  • Performed immunohistochemistry on osteosarcoma tissue microarrays (TMA).
  • Employed small interfering RNA (siRNA) for TOPK silencing and a selective inhibitor (OTS514) for functional studies.

Main Results:

  • TOPK expression was significantly elevated in osteosarcoma compared to normal tissues.
  • High TOPK expression correlated with shorter overall survival, metastasis, and advanced disease status.
  • TOPK inhibition reduced osteosarcoma cell viability, proliferation, migration, and spheroid growth.
  • Combined treatment with OTS514 and chemotherapy (doxorubicin or cisplatin) demonstrated synergistic effects.

Conclusions:

  • TOPK is overexpressed in osteosarcoma and serves as a potential prognostic indicator.
  • Targeting TOPK with inhibitors like OTS514 presents a promising therapeutic strategy for osteosarcoma.
  • TOPK inhibition enhances sensitivity to conventional chemotherapeutic agents in osteosarcoma.
Keywords:
TOPKimmunohistochemistryosteosarcomaprognostic biomarker

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