Expression and role of the embryonic protein SOX2 in head and neck squamous cell carcinoma.

Détails

ID Serval
serval:BIB_E804FAE063EF
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Expression and role of the embryonic protein SOX2 in head and neck squamous cell carcinoma.
Périodique
Carcinogenesis
Auteur(s)
Schröck A., Bode M., Göke F.J., Bareiss P.M., Schairer R., Wang H., Weichert W., Franzen A., Kirsten R., van Bremen T., Queisser A., Kristiansen G., Heasley L., Bootz F., Lengerke C., Perner S.
ISSN
1460-2180 (Electronic)
ISSN-L
0143-3334
Statut éditorial
Publié
Date de publication
07/2014
Peer-reviewed
Oui
Volume
35
Numéro
7
Pages
1636-1642
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Résumé
Recently, SOX2 has been identified as a potential lineage-specific oncogene in lung squamous cell carcinomas. Since head and neck squamous cell carcinomas (HNSCC) are morphologically and clinically highly related to lung squamous cell carcinomas, we hypothesized that SOX2 also plays an oncogenic role in this tumor entity. We assembled a cohort of 496 patients with HNSCC, including 253 metastases and 135 recurrences. SOX2 amplification (FISH) and SOX2 protein expression (immunohistochemistry) were correlated with molecular and clinicopathological parameters. In order to investigate the functional role of SOX2 in human HNSCC, SOX2 knockdown and overexpression in SCC-25 cells were generated by lentiviral constructs and subjected to cell cycle analysis, proliferation and apoptosis assays. Furthermore, SOX2 expression was correlated with the expression of proliferation and apoptosis-related proteins in primary HNSCC samples. SOX2 amplification was detected in 21% of primary HNSCC and mostly observed in a concordant manner between primary tumors and corresponding metastatic tissues. Overall, SOX2 amplification resulted in protein overexpression and was mutually exclusive with human papillomavirus infection. SOX2 protein overexpression was associated with clinicopathological parameters of worse outcome. Functionally, SOX2 induced the expression of the antiapoptotic protein BCL-2 and enhanced resistance to apoptosis-inducing agents including cisplatin, indicating SOX2 as a mediator of therapy resistance in human HNSCC. Targeting SOX2 and related molecular downstream pathways such as BCL-2 may enhance therapy efficacy in SOX2-expressing HNSCC.
Mots-clé
Apoptosis, Biomarkers, Tumor/genetics, Biomarkers, Tumor/metabolism, Blotting, Western, Carcinoma, Squamous Cell/genetics, Carcinoma, Squamous Cell/metabolism, Carcinoma, Squamous Cell/secondary, Cell Proliferation, Cohort Studies, Female, Follow-Up Studies, Head and Neck Neoplasms/genetics, Head and Neck Neoplasms/metabolism, Head and Neck Neoplasms/pathology, Humans, Immunoenzyme Techniques, In Situ Hybridization, Fluorescence, Lymphatic Metastasis, Male, Middle Aged, Neoplasm Grading, Neoplasm Recurrence, Local/genetics, Neoplasm Recurrence, Local/metabolism, Neoplasm Recurrence, Local/pathology, Neoplasm Staging, Prognosis, RNA, Messenger/genetics, Real-Time Polymerase Chain Reaction, Reverse Transcriptase Polymerase Chain Reaction, SOXB1 Transcription Factors/genetics, SOXB1 Transcription Factors/metabolism, Survival Rate, Tumor Cells, Cultured
Pubmed
Web of science
Open Access
Oui
Création de la notice
07/05/2019 10:14
Dernière modification de la notice
21/08/2019 5:36
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