Loss of SOX2 expression induces cell motility via vimentin up-regulation and is an unfavorable risk factor for survival of head and neck squamous cell carcinoma

被引：61

作者：

Bayo, Pilar ^{[1
,2
]}

Jou, Adriana ^{[3
,4
,5
]}

Stenzinger, Albrecht ^{[6
]}

Shao, Chunxuan ^{[7
]}

Gross, Madeleine ^{[3
,4
]}

Jensen, Alexandra ^{[8
]}

Grabe, Niels ^{[9
,10
]}

Mende, Christel Herold ^{[11
,12
]}

Rados, Pantelis Varvaki ^{[5
]}

Debus, Juergen ^{[8
]}

Weichert, Wilko ^{[6
]}

Plinkert, Peter K. ^{[1
]}

Lichter, Peter ^{[4
]}

Freier, Kolja ^{[3
]}

Hess, Jochen ^{[1
,2
]}

机构：

[1] Univ Heidelberg Hosp, Dept Otolaryngol Head & Neck Surg, D-69120 Heidelberg, Germany

[2] German Canc Res Ctr, Res Grp Mol Mech Head & Neck Tumors, D-69120 Heidelberg, Germany

[3] Univ Heidelberg Hosp, Dept Oral & Maxillofacial Surg, D-69120 Heidelberg, Germany

[4] German Canc Res Ctr, Div Mol Genet, D-69120 Heidelberg, Germany

[5] Univ Fed Rio Grande do Sul, Oral Pathol, BR-90035003 Porto Alegre, RS, Brazil

[6] Univ Heidelberg Hosp, Inst Pathol, D-69120 Heidelberg, Germany

[7] German Canc Res Ctr, Div Theoret Syst Biol, D-69120 Heidelberg, Germany

[8] Univ Heidelberg Hosp, Dept Radiat Oncol, D-69120 Heidelberg, Germany

[9] BIOQUANT, Hamamatsu Tissue Imaging & Anal Ctr TIGA, D-69120 Heidelberg, Germany

[10] Natl Ctr Tumor Dis NCT, Med Oncol, Heidelberg, Germany

[11] Univ Heidelberg Hosp, Dept Neurosurg, Expt Neurosurg, D-69120 Heidelberg, Germany

[12] Dept Otorhinolaryngol Head & Neck Surg, Mol Cell Biol Grp, Heidelberg, Germany

来源：

MOLECULAR ONCOLOGY | 2015年 / 9卷 / 08期

关键词：

Cell motility; Gene expression profiling; Immunohistochemistry; Prognostic biomarker; Tissue microarray; TRANSCRIPTION FACTOR SOX2; CANCER STEM-CELLS; PROGNOSTIC-SIGNIFICANCE; 3Q26-29; AMPLICON; POOR-PROGNOSIS; PROMOTES; GROWTH; AMPLIFICATION; TRANSITION; INVASION;

D O I：

10.1016/j.molonc.2015.05.006

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Recurrent gain on chromosome 3q26 encompassing the gene locus for the transcription factor SOX2 is a frequent event in human squamous cell carcinoma, including head and neck squamous cell carcinoma (HNSCC). Numerous studies demonstrated that SOX2 expression and function is related to distinct aspects of tumor cell pathophysiology. However, the underlying molecular mechanisms are not well understood, and the correlation between SOX2 expression and clinical outcome revealed conflicting data. Transcriptional profiling after silencing of SOX2 expression in a HNSCC cell line identified a set of up-regulated genes related to cell motility (e.g. VIM, FN1, CDH2). The inverse regulation of SOX2 and aforementioned genes was validated in 18 independent HNSCC cell lines from different anatomical sites. The inhibition of cell migration and invasion by SOX2 was confirmed by constant or conditional gene silencing and accelerated motility of HNSCC cells after SOX2 silencing was partially reverted by down-regulation of vimentin. In a retrospective study, SOX2 expression was determined by immunohistochemical staining on tissue microarrays containing primary tumor specimens of two independent HNSCC patient cohorts. Low SOX2 expression was found in 19.3% and 44.9% of primary tumor specimens, respectively. Univariate analysis demonstrated a statistically significant correlation between low SOX2 protein levels and reduced progression-free survival (Cohort I 51 vs. 16 months; Cohort II 33 vs. 12 months) and overall survival (Cohort I 150 vs. 37 months; Cohort II 33 vs. 16 months). Multivariate Cox proportional hazard model analysis confirmed that low SOX2 expression serves as an independent prognostic marker for HNSCC patients. We conclude that SOX2 inhibits tumor cell motility in HNSCC cells and that low SOX2 expression serves as a prognosticator to identify HNSCC patients at high risk for treatment failure. (C) 2015 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

引用

页码：1704 / 1719

页数：16

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