SOX2 regulates self-renewal and tumorigenicity of stem-like cells of head and neck squamous cell carcinoma.
SOX2 regulates self-renewal and tumorigenicity of stem-like cells of head and neck squamous cell carcinoma.
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DOI：
10.1038/bjc.2014.528
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发表时间：
2014-11-25
影响因子：
8.8
通讯作者：
Lim, Y. C.
中科院分区：
文献类型：
--
作者：
Lee, S. H.;Oh, S-Y;Do, S. I.;Lee, H. J.;Kang, H. J.;Rho, Y. S.;Bae, W. J.;Lim, Y. C.
头颈部鳞状细胞癌（HNSCC）显示细胞异质性并且含有癌症干细胞（CSC）。性别决定区Y [SRY]-盒（SOX）2是胚胎干细胞命运的重要调节因子，并在几种类型的人类肿瘤中异常表达。尽管如此，SOX 2在HNSCC中的作用仍不清楚。我们从先前建立的HNSCC细胞中产生异位表达SOX 2的细胞，并与对照细胞相比检查这些细胞的细胞增殖、自我更新能力和化疗抗性。此外，我们敲低了从HNSCC肿瘤组织获得的原代球体中的SOX 2，并在体外和体内评估了这些细胞中干细胞相关性状的衰减。此外，我们研究了HNSCC患者中SOX 2表达的临床相关性。SOX 2在HNSCC患者的原发组织中异常表达，但在健康组织中不表达。SOX2表达与HNSCC患者的肿瘤复发和不良预后相关。SOX2的异位表达通过细胞周期蛋白B1的表达和干细胞相关的特征，如自我更新和耐药性，诱导细胞增殖。此外，HNSCC CSC中SOX 2的敲低减弱了它们的自我更新能力、化学抗性（通过ABCG 2抑制）、侵袭能力（通过蜗牛下调）和体内致瘤性。这些结果表明，SOX 2可能在HNSCC的“干性”和进展中起重要作用。靶向SOX2阳性肿瘤细胞（CSC）可能是HNSCCs的一种新的治疗策略。
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. 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. 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. 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.
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影响因子：
4.8
作者：
Rybak, Adrian P.;Tang, Damu
通讯作者：
Tang, Damu
影响因子：
4.7
作者：
Schroeck, Andreas;Bode, Maike;Perner, Sven
通讯作者：
Perner, Sven
DOI：
10.1634/stemcells.2008-0611
发表时间：
2009-02
期刊：
Stem cells (Dayton, Ohio)
影响因子：
--
作者：
Okubo T;Clark C;Hogan BL
通讯作者：
Hogan BL
影响因子：
30.8
作者：
Bass, Adam J.;Watanabe, Hideo;Mermel, Craig H.;Yu, Soyoung;Perner, Sven;Verhaak, Roel G.;Kim, So Young;Wardwell, Leslie;Tamayo, Pablo;Gat-Viks, Irit;Ramos, Alex H.;Woo, Michele S.;Weir, Barbara A.;Getz, Gad;Beroukhim, Rameen;O'Kelly, Michael;Dutt, Amit;Rozenblatt-Rosen, Orit;Dziunycz, Piotr;Komisarof, Justin;Chirieac, Lucian R.;LaFargue, Christopher J.;Scheble, Veit;Wilbertz, Theresia;Ma, Changqing;Rao, Shilpa;Nakagawa, Hiroshi;Stairs, Douglas B.;Lin, Lin;Giordano, Thomas J.;Wagner, Patrick;Minna, John D.;Gazdar, Adi F.;Zhu, Chang Qi;Brose, Marcia S.;Cecconello, Ivan;Ribeiro, Ulysses, Jr.;Marie, Suely K.;Dahl, Olav;Shivdasani, Ramesh A.;Tsao, Ming-Sound;Rubin, Mark A.;Wong, Kwok K.;Regev, Aviv;Hahn, William C.;Beer, David G.;Rustgi, Anil K.;Meyerson, Matthew
通讯作者：
Meyerson, Matthew
影响因子：
23.9
作者：
Sarkar, Abby;Hochedlinger, Konrad
通讯作者：
Hochedlinger, Konrad