Sonic Hedgehog Signalling Activation Contributes to ALCAM Over-Expression and Poor Clinical Outcome in Patients with Oral Squamous Cell Carcinoma
Sonic Hedgehog Signalling Activation Contributes to ALCAM Over-Expression and Poor Clinical Outcome in Patients with Oral Squamous Cell Carcinoma
复制标题
Sonic Hedgehog 信号传导激活导致口腔鳞状细胞癌患者 ALCAM 过度表达和不良临床结果
DOI：
10.3290/j.cjdr.a39916
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发表时间：
2018-01-01
影响因子：
0.9
通讯作者：
Chen, Wan Tao
中科院分区：
文献类型：
--
作者：
Chen, Gang;Yan, Ming;Chen, Wan Tao
目的：为探讨Sonic Hedgehog（SHH）信号分子和活化白细胞粘附分子（ALCAM）在口腔鳞癌（OSCC）侵袭和转移中的作用机制，采用免疫组化方法检测101例OSCC组织中SHH信号分子Gli家族锌指1/2（Gli 1/Gli 2）和ALCAM的表达。结果：Gli 1、Gli 2和ALCAM在101例口腔鳞癌中的表达率分别为54.5%、49.5%和47.5%。ALCAM的高表达与患者群体中较短的生存期相关（P = 0.018），这与其他临床参数无关。值得注意的是，当同时考虑ALCAM表达和阳性淋巴结状态时，实现了对临床结局的增强预测（P = 0.001）。在OSCC细胞系中，ALCAM的下调导致细胞侵袭和转移减少。重要的是，SHH激活增加了ALCAM的半衰期，导致ALCAM积累和增加细胞侵袭和migration.Conclusion：ALCAM过度表达在OSCC中是一个独立的预后因素为OSCC患者。它的过度表达可能是SHH信号通路激活的结果，并有助于OSCC的进展。
Objective: To investigate the Sonic Hedgehog (SHH) signalling molecules and activated leukocyte cell adhesion molecule (ALCAM) expression in the mechanisms regulating invasion and metastasis in oral squamous cell carcinoma (OSCC).Methods: The expressions of SHH signalling molecules Gli family zinc finger 1/2 (Gli1/Gli2), as well as ALCAM expression, was analysed in 101 OSCC patients by immunohistochemistry. The potential relationship between Gli1/Gli2 and ALCAM in regard to invasion and metastasis were studied by western blot, invasion and wound-healing assays.Results: Gli1, Gli2 and ALCAM were expressed in 54.5%, 49.5% and 47.5% of the 101 OSCC specimens, respectively. High expression of ALCAM was associated with shorter survival in the patient population (P = 0.018), which was independent of other clinical parameters. Notably, when both ALCAM expression and positive nodal status were considered, an enhanced prediction of clinical outcomes was achieved (P = 0.001). In OSCC cell lines, down-regulation of ALCAM resulted in reduced cell invasion and metastasis. Importantly, SHH activation increased the half-life of ALCAM leading to ALCAM accumulation and increased cell invasion and migration.Conclusion: ALCAM over-expression in OSCC is an independent prognostic factor for OSCC patients. Its over-expression may be the result of the activation of the SHH signalling pathway and contributes to OSCC progression.