CD100-plexin-B1 induces epithelial-mesenchymal transition of head and neck squamous cell carcinoma and promotes metastasis
CD100-plexin-B1 induces epithelial-mesenchymal transition of head and neck squamous cell carcinoma and promotes metastasis
复制标题
CD100-plexin-B1诱导头颈部鳞状细胞癌上皮间质转化并促进转移
DOI：
10.1016/j.canlet.2019.04.013
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发表时间：
2019
期刊：
影响因子：
9.7
通讯作者：
Li Wei
中科院分区：
文献类型：
--
作者：
Zhang Chen;Qiao Hongjiang;Guo Weinan;Liu Yuan;Yang Luting;Liu Yufeng;Jin Boquan;Fu Meng;Wang Gang;Li Wei
头颈鳞状细胞癌（HNSCC）是最致命的癌症之一，主要是由于高转移率。我们发现HNSCC中CD100的表达水平与肿瘤的T分型、病理分级和淋巴结转移呈正相关。 HNSCC患者血清中可溶性CD100（sCD100）水平显着升高，并且sCD100通过其受体Plexin-B1（PlxnB1）显着诱导HNSCC上皮-间质转化（EMT），并促进异种移植小鼠模型中的转移。此外，sCD100 通过调节 Vav1-Rac1/RhoA-p21 激活激酶途径诱导 EMT 来促进 Snail 的稳定。抗CD100抗体消除CD100诱导的EMT并阻止HNSCC的转移，并且抗CD100抗体还增加HNSCC的药物敏感性。综上所述，我们的研究首次表明CD100诱导HNSCC的EMT并促进转移，CD100将成为HNSCC新型预后生物标志物和潜在治疗靶点的候选者。
Head and neck squamous cell carcinoma (HNSCC) is one of the most lethal cancers mainly due to the high rate of metastasis. Here, we find that the expression level of CD100 in HNSCC is positively correlated with the T category, pathological grade and lymph node metastasis of the tumor. The level of soluble CD100 (sCD100) is highly increased in serum of HNSCC patients, and sCD100 markedly induces the epithelial-mesenchymal transition (EMT) of HNSCC through its receptor, Plexin-B1 (PlxnB1), and promotes the metastasis in a xenograft mouse model. Furthermore, sCD100 promotes the stabilization of Snail through the regulation of the Vav1-Rac1/RhoA-p21-activated kinase pathway for the induction of EMT. Anti-CD100 antibody abolishes the CD100-induced EMT and prevents the metastasis of HNSCC, and anti-CD100 antibody also increases the drug sensitivity of HNSCC. Taken together, our study shows for the first time that CD100 induces the EMT of HNSCC and promotes the metastasis, and CD100 would be a candidate as a novel prognostic biomarker and a potential therapeutic target for HNSCC.