title: Expression and role of the embryonic protein SOX2 in head and neck squamous cell carcinoma.
abstract: 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.
authors.affiliation: Department of Otorhinolaryngology/Head and Neck Surgery, University Hospital of Bonn, 53127 Bonn, Germany, Department of Prostate Cancer Research, Institute of Pathology, University Hospital of Bonn, Sigmund-Freud-Str. 25, 53127 Bonn, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Schröck
authors.affiliation: Department of Prostate Cancer Research, Institute of Pathology, University Hospital of Bonn, Sigmund-Freud-Str. 25, 53127 Bonn, Germany.
authors.forename: Maike
authors.initials: M
authors.lastname: Bode
authors.affiliation: Department of Prostate Cancer Research, Institute of Pathology, University Hospital of Bonn, Sigmund-Freud-Str. 25, 53127 Bonn, Germany.
authors.forename: Friederike Johanna Maria
authors.initials: FJ
authors.lastname: Göke
authors.affiliation: Medical Center II, University Hospital of Tuebingen, 72076 Tuebingen, Germany.
authors.forename: Petra Marion
authors.initials: PM
authors.lastname: Bareiss
authors.affiliation: Medical Center II, University Hospital of Tuebingen, 72076 Tuebingen, Germany.
authors.forename: Rebekka
authors.initials: R
authors.lastname: Schairer
authors.affiliation: Medical Center II, University Hospital of Tuebingen, 72076 Tuebingen, Germany.
authors.forename: Hui
authors.initials: H
authors.lastname: Wang
authors.affiliation: Institute of Pathology, University Hospital of Heidelberg, 69120 Heidelberg, Germany and.
authors.forename: Wilko
authors.initials: W
authors.lastname: Weichert
authors.affiliation: Department of Prostate Cancer Research, Institute of Pathology, University Hospital of Bonn, Sigmund-Freud-Str. 25, 53127 Bonn, Germany.
authors.forename: Alina
authors.initials: A
authors.lastname: Franzen
authors.affiliation: Department of Prostate Cancer Research, Institute of Pathology, University Hospital of Bonn, Sigmund-Freud-Str. 25, 53127 Bonn, Germany.
authors.forename: Robert
authors.initials: R
authors.lastname: Kirsten
authors.affiliation: Department of Otorhinolaryngology/Head and Neck Surgery, University Hospital of Bonn, 53127 Bonn, Germany.
authors.forename: Tobias
authors.initials: T
authors.lastname: van Bremen
authors.affiliation: Department of Prostate Cancer Research, Institute of Pathology, University Hospital of Bonn, Sigmund-Freud-Str. 25, 53127 Bonn, Germany.
authors.forename: Angela
authors.initials: A
authors.lastname: Queisser
authors.affiliation: Department of Prostate Cancer Research, Institute of Pathology, University Hospital of Bonn, Sigmund-Freud-Str. 25, 53127 Bonn, Germany.
authors.forename: Glen
authors.initials: G
authors.lastname: Kristiansen
authors.affiliation: Department of Craniofacial Biology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
authors.forename: Lynn
authors.initials: L
authors.lastname: Heasley
authors.affiliation: Department of Otorhinolaryngology/Head and Neck Surgery, University Hospital of Bonn, 53127 Bonn, Germany.
authors.forename: Friedrich
authors.initials: F
authors.lastname: Bootz
authors.affiliation: Medical Center II, University Hospital of Tuebingen, 72076 Tuebingen, Germany.
authors.forename: Claudia
authors.initials: C
authors.lastname: Lengerke
authors.affiliation: Department of Prostate Cancer Research, Institute of Pathology, University Hospital of Bonn, Sigmund-Freud-Str. 25, 53127 Bonn, Germany, sven.perner1972@googlemail.com.
authors.forename: Sven
authors.initials: S
authors.lastname: Perner
mesh_terms: D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism* / Q000556:secondary; D049109:Cell Proliferation; D015331:Cohort Studies; D005260:Female; D005500:Follow-Up Studies; D006258:Head and Neck Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007124:Immunoenzyme Techniques; D017404:In Situ Hybridization, Fluorescence; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009364:Neoplasm Recurrence, Local / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D009367:Neoplasm Staging; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D055748:SOXB1 Transcription Factors / Q000235:genetics / Q000378:metabolism*; D015996:Survival Rate; D014407:Tumor Cells, Cultured
chemical_list: D014408:Biomarkers, Tumor; D012333:RNA, Messenger; C527782:SOX2 protein, human; D055748:SOXB1 Transcription Factors