Expression and role of the embryonic protein SOX2 in head and neck squamous cell carcinoma
Expression and role of the embryonic protein SOX2 in head and neck squamous cell carcinoma
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DOI：
10.1093/carcin/bgu094
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发表时间：
2014-07-01
期刊：
影响因子：
4.7
通讯作者：
Perner, Sven
中科院分区：
文献类型：
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作者：
Schroeck, Andreas;Bode, Maike;Perner, Sven
最近，SOX2已被确定为肺鳞状细胞癌的潜在谱系特异性癌基因。由于头颈部鳞状细胞癌（HNSCC）在形态学和临床上与肺鳞状细胞癌高度相关，我们假设SOX2在这种肿瘤实体中也起致瘤作用。我们收集了496例HNSCC患者，包括253例转移和135例复发。SOX2扩增（FISH）和SOX2蛋白表达（免疫组化）与分子和临床病理参数相关。为了研究SOX2在人HNSCC中的功能作用，我们利用慢病毒构建方法在SCC-25细胞中产生SOX2的低表达和过表达，并进行细胞周期分析、增殖和凋亡实验。此外，在原发性HNSCC中，SOX2的表达与增殖和凋亡相关蛋白的表达相关。在21%的原发性HNSCC中检测到SOX2扩增，并且在原发肿瘤和相应的转移组织中大多以一致的方式观察到。总的来说，SOX2扩增导致蛋白过表达，并且与人乳头瘤病毒感染相互排斥。SOX2蛋白过表达与预后较差的临床病理参数相关。功能上，SOX2诱导抗凋亡蛋白BCL-2的表达，增强对包括顺铂在内的凋亡诱导药物的耐药性，表明SOX2是人HNSCC治疗耐药的中介。靶向SOX2及相关分子下游通路如BCL-2可能提高SOX2表达的HNSCC的治疗效果。
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.