Slug is a key mediator of hypoxia induced cadherin switch in HNSCC: correlations with poor prognosis.
Slug is a key mediator of hypoxia induced cadherin switch in HNSCC: correlations with poor prognosis.
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DOI：
10.1016/j.oraloncology.2013.08.003
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发表时间：
2013-11
期刊：
影响因子：
4.8
通讯作者：
Jiali Zhang;Q. Cheng;Yi Zhou;Yu Wang;Xinming Chen
中科院分区：
文献类型：
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作者：
Jiali Zhang;Q. Cheng;Yi Zhou;Yu Wang;Xinming Chen
目的近年来的研究表明，Slug在缺氧诱导的钙粘蛋白转换中的作用因肿瘤而异。Slug是否是头颈部鳞状细胞癌（HNSCC）中肿瘤缺氧诱导的钙粘蛋白转换的重要介质以及Slug在HNSCC患者中的预后作用尚未阐明。本研究的目的是探讨Slug在缺氧诱导的HNSCC钙粘蛋白转换中的作用。材料与方法本实验选用2株HNSCC细胞系和119例HNSCC标本。体外检测E/N-cadherins的表达和缺氧/HIF-1α过表达以及Slug/SnaI 2基因沉默对肿瘤细胞侵袭的影响。通过免疫组织化学染色分析HNSCC标本，以将Slug、HIF-1α和E/N-cadherins的表达与临床结果联系起来。结果和结论我们的研究证明，缺氧/HIF-1α过表达后，HNSCC细胞中Slug的表达急剧升高。抑制Slug表达可损害HIF-1α诱导的钙粘蛋白转换和肿瘤侵袭。在HNSCC组织中，检测到Slug的相对高表达与内源性HIF-1α过表达、钙粘蛋白转换、淋巴结转移的风险以及更晚期的TNM分期相关。此外，Slug异常表达与HIF-1α过表达和钙粘蛋白转换联合与HNSCC患者生存期缩短显著相关。总之，Slug是HNSCC缺氧诱导的钙粘蛋白转换所必需的，并可作为预测HNSCC临床结局的潜在风险标志物。
ObjectivesAccording to recent studies, the function of Slug in hypoxia induced cadherin switch differs from cancer to cancer. Whether Slug is an essential mediator of the tumor hypoxia induced cadherin switch in head and neck squamous cell carcinoma (HNSCC) and the prognostic role of Slug in HNSCC patients are not elucidated. The aim of this study is to investigate the role of the Slug in cadherin switch induced by hypoxia in HNSCC.Materials and methodsTwo HNSCC cell lines and 119 HNSCC specimens were selected for the present experiments. E/N-cadherins expression and tumor cell invasion responding to hypoxia/HIF-1α overexpression and the silence of Slug/SnaI2 gene were detectedin vitro.HNSCC specimens were analyzed by immunohistochemistry staining to correlate the expressions of Slug, HIF-1α and E/N-cadherins with clinical outcomes.Results and conclusionOur research evidenced that Slug was extremely elevated in the HNSCC cells in response to hypoxia/HIF-1α overexpression. Suppressing Slug expression impaired HIF-1α induced cadherin switch and tumor invasion. In HNSCC tissues, relatively high expression of Slug was detected to be associated with endogenous HIF-1α overexpression, cadherin switch, the risk of lymph node metastasis, and a more advanced TNM stage. Additionally, aberrant Slug expression combined with HIF-1α overexpression and cadherin switch was significantly correlated with shorter HNSCC patient survival. In conclusion, Slug is necessary for hypoxia-induced cadherin switch in HNSCC and may be used as a potential risk marker in predicting HNSCC clinical outcomes.