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Updated: Jan 19, 2026

A Syngeneic Orthotopic Osteosarcoma Sprague Dawley Rat Model with Amputation to Control Metastasis Rate
Published on: May 3, 2021
CSN5 controls the growth of osteosarcoma via modulating the EGFR/PI3K/Akt axis
Zongmiao Wan1, Sheng Huang1, Fengbo Mo1
1Department of Orthopedic Surgery, First Affiliated Hospital of Nanchang University, Nanchang, 330006, China.
Abstract:
CSN5, a critical subunit of the constitutive photomorphogenesis 9 (COP9) signalosome (CSN), functions as a potential tumor promoter in various cancers. However, the biological functions and clinical significance of CSN5 in osteosarcoma (OS) remains unclear. Here, we report that OS tumors overexpressed CSN5 compared with normal bone tissues, and CSN5 overexpression was obviously associated with the malignant phenotype and poor prognosis in patients with OS. In addition, high CSN5 expression significantly promoted the growth of OS cells, whereas CSN5 silence suppressed the tumorigenicity of OS cells. Furthermore, we found PI3K/Akt signaling pathway contributed to the effects of CSN5 in OS cells, and blocking the Akt pathway significantly inhibited the actions of CSN5. Mechanistically, we demonstrate that CSN5 positively regulated EGFR stability through reducing the levels of EGFR ubiquitination, thereby activating the PI3K/Akt signaling pathway in OS cells. Moreover, our results shown that the oncogenic effects of CSN5 on OS cells were EGFR dependent. Thus, CSN5 has a central role in regulating diverse aspects of the pathogenesis of OS, which could be a potential diagnostic and therapeutic target for OS.
Insights
Constitutive photomorphogenesis 9 signalosome subunit 5 (CSN5) promotes osteosarcoma growth by stabilizing EGFR, activating the PI3K/Akt pathway. CSN5 overexpression correlates with poor prognosis, suggesting it as a potential diagnostic and therapeutic target for osteosarcoma.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- The constitutive photomorphogenesis 9 signalosome (CSN) subunit CSN5 is implicated in various cancers.
- The role of CSN5 in osteosarcoma (OS) pathogenesis and its clinical significance remain largely unknown.
Purpose of the Study:
- To investigate the biological functions and clinical relevance of CSN5 in osteosarcoma.
- To elucidate the underlying molecular mechanisms of CSN5's action in OS.
Main Methods:
- Comparative analysis of CSN5 expression in OS tumors versus normal bone tissues.
- In vitro and in vivo studies assessing the impact of CSN5 overexpression and silencing on OS cell growth and tumorigenicity.
- Investigation of the involvement of the PI3K/Akt signaling pathway and epidermal growth factor receptor (EGFR) in CSN5-mediated effects.
Main Results:
- CSN5 is overexpressed in OS tumors and associated with malignant phenotypes and poor patient prognosis.
- High CSN5 expression promotes OS cell growth and tumorigenicity, while CSN5 silencing inhibits these processes.
- CSN5 activates the PI3K/Akt pathway, and its oncogenic effects are dependent on EGFR stabilization via reduced ubiquitination.
Conclusions:
- CSN5 plays a crucial role in osteosarcoma development and progression.
- CSN5's regulation of EGFR stability and subsequent activation of the PI3K/Akt pathway are key mechanisms in OS pathogenesis.
- CSN5 represents a promising diagnostic biomarker and therapeutic target for osteosarcoma.
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