Related Experiment Video
Updated: Oct 13, 2025
A Syngeneic Orthotopic Osteosarcoma Sprague Dawley Rat Model with Amputation to Control Metastasis Rate
Published on: May 3, 2021
Hsp90 regulates the tumorigenic function of tyrosine protein kinase in osteosarcoma
Zhao-Peng Yao1, Hui Zhu2, Feng Shen1
1Department of Orthopaedics, The First Hospital of Nanchang, Nanchang, China.
Abstract:
Despite recent advances in diagnosis and treatment, osteosarcoma remains as the most common bone cancer in children and is associated with poor prognosis. Growing evidence has supported dysregulation of threonine and tyrosine protein kinase (TTK) expression as a hallmark of multiple cancers, however, its function in osteosarcoma remains to be elucidated. In the present study, we found that TTK was frequently overexpressed in osteosarcoma and associated with increased tumour growth and progression. Moreover, using both in vitro and in vivo assays, we provided evidence that TTK level was regulated by a molecular chaperone, heat shock protein 90 (Hsp90). Hsp90 directly interacted with TTK and prevents proteasome-dependent TTK degradation, leading to the accumulation of TTK in osteosarcoma cells. Elevated TTK promoted cancer cell proliferation and survival by activating cell-cycle progression and inhibiting apoptosis. Consistently, depletion of TTK by Hsp90 inhibition induced cell-cycle arrest, generated aneuploidy and eventually resulted in apoptotic cancer cell death. Together, our study revealed an important Hsp90-TTK regulatory axis in osteosarcoma cells to promote cancer cell growth and survival. These findings expand our knowledge on osteosarcoma pathogenesis and offer novel therapeutic options for clinical practice.
Insights
Heat shock protein 90 (Hsp90) stabilizes threonine and tyrosine protein kinase (TTK) in osteosarcoma, promoting cancer growth. Inhibiting Hsp90 reduces TTK, halting cell-cycle progression and inducing cancer cell death.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Osteosarcoma is a prevalent pediatric bone cancer with a poor prognosis.
- Threonine and tyrosine protein kinase (TTK) dysregulation is implicated in various cancers, but its role in osteosarcoma is unclear.
Purpose of the Study:
- To investigate the role and regulation of TTK in osteosarcoma.
- To elucidate the functional impact of TTK on osteosarcoma cell proliferation and survival.
Main Methods:
- Quantitative analysis of TTK expression in osteosarcoma tissues.
- In vitro and in vivo assays to study TTK regulation by heat shock protein 90 (Hsp90).
- Assessment of cell-cycle progression, apoptosis, and aneuploidy following TTK modulation.
Main Results:
- TTK was frequently overexpressed in osteosarcoma, correlating with tumor progression.
- Hsp90 directly binds TTK, inhibiting its proteasomal degradation and causing TTK accumulation.
- Elevated TTK enhanced osteosarcoma cell proliferation and survival by promoting cell-cycle progression and inhibiting apoptosis.
- Hsp90 inhibition led to TTK depletion, inducing cell-cycle arrest, aneuploidy, and apoptosis.
Conclusions:
- An Hsp90-TTK regulatory axis promotes osteosarcoma cell growth and survival.
- Targeting this axis offers a potential therapeutic strategy for osteosarcoma.
- Findings provide insights into osteosarcoma pathogenesis and potential clinical interventions.
Related Concept Videos
03:03mTOR Signaling and Cancer Progression
The mTOR pathway or the...
01:22PI3K/mTOR/AKT Signaling Pathway
02:23Abnormal Proliferation
01:20The JAK-STAT Signaling Pathway
01:24Regulation of Angiogenesis and Blood Supply
01:15Receptor Downregulation in MVBs
The EGFR can initiate signaling pathways that lead to cell proliferation, migration, and differentiation. Overexpression of EGFR stimulates cells to proliferate. Excessive EGFR...