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Carboxy-terminus Hsc70 interacting protein exerts a tumor inhibition function in head and neck cancer
Meng Xiao1, Ming Yan1, Jianjun Zhang1
1Department of Oral and Maxillofacial-Head and Neck Oncology, Ninth People's Hospital, Shanghai Jiaotong University, School of Medicine, Shanghai 200011, P.R. China.
Abstract:
Several independent studies have reported the roles of the E3 ubiquitin ligase, carboxy-terminus Hsc70 interacting protein (CHIP) in various types of cancers. However, the biological effects of CHIP vary in regards to different cancers, and the role of CHIP in head and neck cancers (HNCs) remains unknown. In the present study, CHIP overexpression plasmids and CHIP knockdown lentivirus were constructed to affect the expression levels of CHIP protein and biological behaviors in HNC cell lines bilaterally. The biological behaviors regulated by CHIP in HNCs were investigated both in vivo and in vitro with a series of assays and analyses. A tissue microarray was stained and analyzed for the clinical significance of CHIP expression in HNCs. We identified that CHIP suppressed the malignant behaviors of HNCs in a series of in vitro and in vivo experiments, but not its two loss-of-function mutants. However, we observed an altered expression pattern of CHIP from a well, moderate, to poor differentiation pathological status in HNC specimens. In a retrospective cohort of HNCs, lower expression of CHIP indicated a poor differentiation status in tumors and a lower overall survival rate. The present study demonstrated that CHIP functions as a tumor suppressor in HNCs. In conclusion, we demonstrated that suppressed expression of CHIP may result in the progression of HNCs.
Insights
The carboxy-terminus Hsc70 interacting protein (CHIP) acts as a tumor suppressor in head and neck cancers (HNCs). Lower CHIP expression correlates with poor tumor differentiation and reduced survival rates in HNC patients.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- The E3 ubiquitin ligase, carboxy-terminus Hsc70 interacting protein (CHIP), has known roles in various cancers, but its function in head and neck cancers (HNCs) is uncharacterized.
- Understanding CHIP's role is crucial for developing targeted therapies for HNCs.
Purpose of the Study:
- To investigate the biological effects and clinical significance of CHIP in head and neck cancers.
- To determine if CHIP functions as an oncogene or tumor suppressor in HNCs.
Main Methods:
- CHIP expression was manipulated using overexpression plasmids and knockdown lentivirus in HNC cell lines.
- In vitro and in vivo assays were performed to assess the impact of CHIP on HNC biological behaviors.
- Tissue microarrays and retrospective cohort analysis were used to evaluate the clinical significance of CHIP expression in HNC specimens.
Main Results:
- CHIP overexpression suppressed malignant behaviors of HNCs in vitro and in vivo, while loss-of-function mutants did not.
- Altered CHIP expression patterns were observed correlating with tumor differentiation status (well, moderate, poor).
- Lower CHIP expression in HNCs was associated with poor differentiation and decreased overall survival.
Conclusions:
- CHIP functions as a tumor suppressor in head and neck cancers.
- Suppressed CHIP expression may contribute to HNC progression.
- CHIP expression levels have clinical significance and prognostic value in HNCs.
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