2016 Fiscal Year Final Research Report
The mechanism of malignant transformation of CADM1-positive lung adenocarcinoma
| Project/Area Number |
25460432
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Human pathology
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| Research Institution | Jichi Medical University (2015-2016)
The University of Tokyo (2013-2014) |
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Principal Investigator |
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| Project Period (FY) |
2013-04-01 – 2017-03-31
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| Keywords | CADM1 / RAPGEF2 / RAP1 / non-TRU type |
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| Outline of Final Research Achievements |
Some invasive high-grade adenocarcinomas overexpress CADM1. Here, we investigated the characteristics of CADM1-positive high-grade subtype. In this study, we found that lung adenocarcinoma cell lines expressing CADM1 frequently show low level expressions of bronchial epithelial markers. Furthermore, these CADM1-positive cell lines co-express RAPGEF2. Knockdown of RAPGEF2 reduced cell migration and RAP1 activity, which suggested that RAPGEF2 promoted cell migration through activation of RAP1. In addition, our knockdown experiments of RAPGEF2 indicate that RAPGEF2 reduces the tumor suppressor function of CADM1. Immunohistochemical analysis of lung adenocarcinoma cases (n=140) revealed that high level expression of RAPGEF2 correlated with high-grade subtype, low level expressions of bronchial epithelial markers, and worse prognosis especially in CADM1-positive lung adenocarcinomas. In conclusion, RAPGEF2 will get involved in the malignant phenotype of CADM1-positive high grade subtype.
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| Free Research Field |
肺癌
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