2006 Fiscal Year Final Research Report Summary
Snail-induced downregulation of deltaNp63 acquires invasive phenotype of human squamous cell carcinoma
| Project/Area Number |
17592085
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Surgical dentistry
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| Research Institution | HIROSHIMA UNIVERSITY |
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Principal Investigator |
HIGASHIKAWA Koichiro Hiroshima University, Graduate school of Biomedical Science, Research Associate, 大学院医歯薬学総合研究科, 助手 (80363084)
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| Co-Investigator(Kenkyū-buntansha) |
KAMATA Nobuyuki Hiroshima University, Graduate school of Biomedical Science, Professor, 大学院医歯薬学総合研究科, 教授 (70242211)
ONO Shigehiro Hiroshima University, Graduate school of Biomedical Science, Research Associate, 大学院医歯薬学総合研究科, 助手 (70379882)
SHIGEISHI Hideo Hiroshima University, Graduate school of Biomedical Science, Research Associate, 大学院医歯薬学総合研究科, 助手 (90397943)
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| Project Period (FY) |
2005 – 2006
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| Keywords | Oral Cancer / EMT / Tumor Invasion and Metastasis / p63 |
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| Research Abstract |
p63 is a member of the p53 family and regulates crucial events in the formation of epithelial structures, but the role of p63 in tumor is unclear. We found that Snail-induced epithelial-to-mesenchymal transition (EMT) is accompanied by downregulation of p63 in human squamous cell carcinomas (SCCs). deltaNp63alpha is the predominantly expressed p63 isoform in SCC cells. deltaNp63 promoter activity required a C/EBP binding element and was reduced remarkably by Snail. Downregulation of deltaNp63alpha and reduction of C/EBPalpha were observed in EMT-phenotype cells, which exhibited invasive activity in vitro. p63 knockdown in cells enhanced invasive activity in the presence of E-cadherin. Conversely, forced expression of deltaNp63alpha blocked invasive activity of cells with the EMT phenotype. These findings indicate that Snail downregulates deltaNp63alpha, leading to acquisition of the invasive phenotype by SCC. The invasive activity caused by downregulation of deltaNp63alpha does not require downregulation of E-cadherin.
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