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Updated: Feb 27, 2026
Next Generation Sequencing for the Detection of Actionable Mutations in Solid and Liquid Tumors
Published on: September 20, 2016
Functional analysis of Discoidin domain receptor 2 mutation and expression in squamous cell lung cancer
Naomi Kobayashi-Watanabe1, Akemi Sato2, Tatsuro Watanabe3
1Division of Hematology, Respiratory Medicine and Oncology, Department of Internal Medicine, Faculty of Medicine, Saga University, 5-1-1 Nabeshima, Saga 849-8501, Japan.
Objectives:
Discoidin domain receptor (DDR) 2 mutations have recently been reported to be candidate targets of molecular therapy in lung squamous cell carcinoma (SQCC). However, the status of DDR2 expression and mutations, as well as their precise roles in lung SQCC, have not been clarified. We here report DDR2 mutation and expression status in clinical samples and its role of lung SQCC.
Materials And Methods:
We investigated DDR2 expression and mutation status in 44 human clinical samples and 7 cell lines. Biological functions of DDR2 were assessed by in vitro cell invasion assay and animal model experiments.
Results:
Endogenous DDR2 protein expression levels were high in one cell line, PC-1, and immunohistochemistry of lung cancer tissue array showed high levels of DDR2 protein in 29% of lung SQCC patients. A mutation (T681I) identified in lung SQCC and the cell line EBC-1 was detected among 44 primary lung SQCC samples and 7 lung SQCC cell lines. Although Forced expression of DDR2 and its mutant (T681I) led to induce SQCC cell invasion in vitro, only wild type DDR2 enhanced lung metastasis in an animal model. We also found that ectopic expression of DDR2 induced MMP-1 mRNA expression accompanied by phosphorylation of c-Jun after treatment with its ligand, collagen type I, but DDR2 with the T681I mutation did not, suggesting that T681I mutation is an inactivating mutation.
Conclusion:
Overexpression of DDR2 might contribute to tumor progression in lung SQCC. The overexpression of DDR2 could be potential molecular target of lung SQCC.
Insights
Discoidin domain receptor 2 (DDR2) overexpression may drive lung squamous cell carcinoma (SQCC) progression. This study clarifies DDR2
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Discoidin domain receptor 2 (DDR2) mutations are potential targets for molecular therapy in lung squamous cell carcinoma (SQCC).
- The precise role and expression status of DDR2 in lung SQCC remain unclear.
Purpose of the Study:
- To investigate DDR2 expression and mutation status in clinical lung SQCC samples.
- To elucidate the functional role of DDR2 in lung SQCC progression and metastasis.
Main Methods:
- Analysis of DDR2 expression and mutations in 44 human clinical SQCC samples and 7 cell lines.
- In vitro cell invasion assays and animal model experiments to assess DDR2 function.
- Immunohistochemistry and Western blot analysis to evaluate protein expression and activation.
Main Results:
- High DDR2 protein expression was observed in 29% of lung SQCC patients and specific cell lines.
- A novel DDR2 mutation (T681I) was identified in lung SQCC samples and cell lines.
- Forced expression of wild-type DDR2 promoted in vitro invasion and in vivo lung metastasis, while the T681I mutant showed impaired function, suggesting it is an inactivating mutation.
- Ectopic DDR2 expression induced MMP-1 mRNA and c-Jun phosphorylation upon collagen type I stimulation.
Conclusions:
- DDR2 overexpression is implicated in lung SQCC tumor progression.
- DDR2 represents a potential molecular target for lung SQCC therapy.
