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SOX2 regulates self-renewal and tumorigenicity of stem-like cells of head and neck squamous cell carcinoma

Title
SOX2 regulates self-renewal and tumorigenicity of stem-like cells of head and neck squamous cell carcinoma
Authors
Lee S.H.Oh S.-Y.Do S.I.Lee H.J.Kang H.J.Rho Y.S.Bae W.J.Lim Y.C.
Ewha Authors
노영수
SCOPUS Author ID
노영수scopus
Issue Date
2014
Journal Title
British Journal of Cancer
ISSN
0007-0920JCR Link
Citation
vol. 111, no. 11, pp. 2122 - 2130
Keywords
cancer stem cellhead and neck squamous cell carcinomasSOX2target therapy
Publisher
Nature Publishing Group
Indexed
SCI; SCIE; SCOPUS WOS scopus
Abstract
Background: Head and neck squamous cell carcinomas (HNSCCs) display cellular heterogeneity and contain cancer stem cells (CSCs). Sex-determining region Y SRY-box (SOX)2 is an important regulator of embryonic stem cell fate and is aberrantly expressed in several types of human tumours. Nonetheless, the role of SOX2 in HNSCC remains unclear. Methods: We created cells ectopically expressing SOX2 from previously established HNSCC cells and examined the cell proliferation, self-renewal capacity, and chemoresistance of these cells compared with control cells. In addition, we knocked down SOX2 in primary spheres obtained from HNSCC tumour tissue and assessed the attenuation of stemness-associated traits in these cells in vitro and in vivo. Furthermore, we examined the clinical relevance of SOX2 expression in HNSCC patients. Results: SOX2 is aberrantly expressed in primary tissue of HNSCC patients but not in healthy tissue. SOX2 expression correlated with tumour recurrence and poor prognosis of HNSCC patients. Ectopic expression of SOX2 induced cell proliferation via cyclin B1 expression and stemness-associated features, such as self-renewal and chemoresistance. In addition, a knockdown of SOX2 in HNSCC CSCs attenuated their self-renewal capacity, chemoresistance (through ABCG2 suppression), invasion capacity (via snail downregulation), and in vivo tumorigenicity. Conclusions: These results suggest that SOX2 may have important roles in the 'stemness' and progression of HNSCC. Targeting SOX2-positive tumour cells (CSCs) could be a new therapeutic strategy in HNSCCs. © 2014 Cancer Research UK.
DOI
10.1038/bjc.2014.528
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의과대학 > 의학과 > Journal papers
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