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

Schrock, Andreas and Bode, Maike and Goke, Friederike Johanna Maria and Bareiss, Petra Marion and Schairer, Rebekka and Wang, Hui and Weichert, Wilko and Franzen, Alina and Kirsten, Robert and van Bremen, Tobias and Queisser, Angela and Kristiansen, Glen and Heasley, Lynn and Bootz, Friedrich and Lengerke, Claudia and Perner, Sven. (2014) Expression and role of the embryonic protein SOX2 in head and neck squamous cell carcinoma. Carcinogenesis, 35 (7). pp. 1636-1642.

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Official URL: https://edoc.unibas.ch/62316/

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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.
Faculties and Departments:03 Faculty of Medicine > Departement Biomedizin > Department of Biomedicine, University Hospital Basel > Stem Cells and Hematopoiesis (Lengerke)
UniBasel Contributors:Lengerke, Claudia
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Oxford University Press
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:15 Dec 2020 11:10
Deposited On:15 Dec 2020 11:10

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