Oncogene, 2007-03, Vol.26 (10), p.1459-1467
2007
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- Autor(en) / Beteiligte
- Titel
- Overexpression of NBS1 induces epithelial-mesenchymal transition and co-expression of NBS1 and Snail predicts metastasis of head and neck cancer
- Ist Teil von
- Oncogene, 2007-03, Vol.26 (10), p.1459-1467
- Ort / Verlag
- Basingstoke: Nature Publishing
- Erscheinungsjahr
- 2007
- Quelle
- Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals
- Beschreibungen/Notizen
- Major causes of head and neck squamous cell carcinoma (HNSCC)-related deaths are cervical node and distant metastasis. We previously demonstrated that overexpression of the DNA double-strand break repair protein Nijmegen breakage syndrome 1 (NBS1) is a prognostic marker of advanced HNSCCs. Epithelial-mesenchymal transition (EMT) was demonstrated to be the major mechanism responsible for mediating invasiveness and metastasis of late-stage cancers. We therefore investigated the role of NBS1 overexpression in mediating EMT and metastasis. NBS1 overexpression was associated with metastasis of HNSCC patients using tissue microarray-immunohistochemistry approach. Induction of EMT was observed in an NBS1-overexpressing HNSCC cell line (FADUNBS), whereas short-interference RNA (siRNA)-mediated repression of endogenous NBS1 reversed the shift of EMT markers. Increased migration/invasiveness of FADUNBS was shown by in vitro and in vivo assays. NBS1 overexpression upregulated the expression of an EMT regulator Snail and its downstream target matrix metalloproteinase-2. EMT phenotypes and increased migration/invasiveness of FADUNBS cells were reversed by siRNA-mediated repression of Snail expression or a phosphatidylinositol 3-kinase-specific inhibitor. In HNSCC samples, co-expression of NBS1/Snail in primary tumors correlated with metastasis and the worst prognosis. These results indicate that NBS1 overexpression induces EMT through the upregulation of Snail expression, and co-expression of NBS1/Snail predicts metastasis in HNSCCs.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0950-9232eISSN: 1476-5594DOI: 10.1038/sj.onc.1209929Titel-ID: cdi_proquest_miscellaneous_70225439
- Format
- –
- Schlagworte
- 1-Phosphatidylinositol 3-kinase, Biological and medical sciences, Cancer, Care and treatment, Cell Cycle Proteins - metabolism, Cell migration, Cell physiology, Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes, Cell Transformation, Neoplastic, Deoxyribonucleic acid, DNA, DNA Breaks, Double-Stranded, DNA damage, DNA microarrays, DNA repair, Double-strand break repair, Enzyme inhibitors, Epithelium, Fundamental and applied biological sciences. Psychology, Gene expression, Genetic aspects, Head & neck cancer, Head and neck cancer, Head and neck carcinoma, Head and Neck Neoplasms - metabolism, Head and Neck Neoplasms - pathology, Humans, Immunohistochemistry, Invasiveness, Matrix metalloproteinase, Matrix Metalloproteinase 2 - metabolism, Medical sciences, Mesenchyme, Mesoderm, Metalloproteinase, Metastases, Metastasis, Molecular and cellular biology, Neoplasm Invasiveness, Neoplasm Metastasis, Neoplasms, Squamous Cell - metabolism, Neoplasms, Squamous Cell - pathology, Nijmegen breakage syndrome, Nuclear Proteins - metabolism, Oncology, Otorhinolaryngology (head neck, general aspects and miscellaneous), Otorhinolaryngology. Stomatology, Pathology, Phenotypes, Prognosis, RNA, Small Interfering - pharmacology, RNA-mediated interference, siRNA, Snail Family Transcription Factors, Squamous cell carcinoma, Transcription Factors - metabolism, Tumor Cells, Cultured, Tumors