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Published on: March 15, 2024
CDH4 inhibits ferroptosis in oral squamous cell carcinoma cells
Jian Xie1,2, Ting Lan1, Da-Li Zheng1
1Department of Preventive Dentistry, School and Hospital of Stomatology, Fujian Medical University, 246 Yang Qiao Middle Road, Fuzhou, 350002, China.
Background:
The cadherin-4 gene (CDH4), a member of the cadherin family genes, encodes R-cadherin (R-cad); however, the function of this gene in different types of cancer remains controversial. The function of CDH4 in OSCC (oral squamous cell carcinoma) is unknown.
Materials And Methods:
We use the Cancer Genome Atlas (TCGA) database to find the expression of CDH4 in OSCC is more than normal tissue. Our tissue samples also confirmed that CDH4 gene was highly expressed in OSCC. The related cell function assay detected that CDH4 promotes the ability of cell proliferation, migration, self-renewal and invasion. Cell staining experiment confirmed that the change of CDH4 expression would change the cell mortality. The western blot of GPX4 (glutathione-dependent peroxidase-4), GSH (reduced glutathione) test assay and MDA(Malondialdehyde) test assay show that the expression of CDH4 may resist the sensitivity of ferropotosis in OSCC.
Results:
CDH4 was upregulated in OSCC samples and was correlation with poor survival of patients. High expression of CDH4 effectively promotes the proliferation, mobility of OSCC cells and reduce the sensitivity of OSCC cells to ferroptosis. CDH4 is positively correlated with EMT pathway genes, negatively correlated with fatty acid metabolism pathway genes and peroxisome pathway genes, and positively correlated with ferroptosis suppressor genes in OSCC.
Conclusions:
These results indicate that CDH4 may play a positive role in tumor progression and resistance ferroptosis and may be a potential therapeutic target for OSCC.
Insights
Cadherin-4 (CDH4) promotes oral squamous cell carcinoma (OSCC) progression and resistance to ferroptosis. High CDH4 expression correlates with poor patient survival, suggesting CDH4 as a potential therapeutic target for OSCC.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Genomics
Background:
- The function of cadherin-4 (CDH4) in various cancers is debated, and its role in oral squamous cell carcinoma (OSCC) is currently unknown.
- CDH4 encodes R-cadherin, a protein involved in cell adhesion.
Purpose of the Study:
- To investigate the role of CDH4 in oral squamous cell carcinoma (OSCC).
- To determine the correlation between CDH4 expression and patient survival, cell proliferation, migration, invasion, and ferroptosis sensitivity in OSCC.
Main Methods:
- Utilized The Cancer Genome Atlas (TCGA) database for gene expression analysis.
- Performed cell function assays, cell staining, western blot, and biochemical tests (GPX4, GSH, MDA) on OSCC tissue samples.
Main Results:
- CDH4 was significantly upregulated in OSCC tissues compared to normal tissues and correlated with poorer patient survival.
- Elevated CDH4 expression enhanced OSCC cell proliferation, migration, self-renewal, and invasion.
- CDH4 expression was associated with reduced sensitivity to ferroptosis and correlated with EMT pathway genes, fatty acid metabolism, peroxisome pathways, and ferroptosis suppressor genes in OSCC.
Conclusions:
- CDH4 plays a crucial role in OSCC progression and confers resistance to ferroptosis.
- CDH4 may serve as a potential therapeutic target for oral squamous cell carcinoma.
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