CCL21/CCR7 interaction promotes EMT and enhances the stemness of OSCC via a JAK2/STAT3 signaling pathway
CCL21/CCR7 interaction promotes EMT and enhances the stemness of OSCC via a JAK2/STAT3 signaling pathway
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CCL21/CCR7 相互作用通过 JAK2/STAT3 信号通路促进 EMT 并增强 OSCC 的干性
DOI：
10.1002/jcp.29525
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发表时间：
2020-02-04
影响因子：
5.6
通讯作者：
Shang, Zhengjun
中科院分区：
文献类型：
--
作者：
Chen, Yang;Shao, Zhe;Shang, Zhengjun
趋化因子及其受体与各种癌症的不良临床结果有很强的关系。然而，其潜在机制仍有待充分阐明。本研究发现C-C趋化因子受体7（CCR 7）及其配体趋化因子配体21（CCL 21）在口腔鳞状细胞癌（OSCC）组织中异常丰富，且CCR 7表达与OSCC预后不良相关。在外源性CCL 21刺激后，OSCC细胞中的上皮-间质转化（EMT）被促进，并且癌干细胞相关标志物CD 133、CD 44、BMI 1、ALDH 1A 1和OCT 4增加。OSCC细胞的迁移、侵袭、成球和集落形成能力增强，表明OSCC细胞的干细胞性也得到改善。CCR 7的敲低和过表达有效地影响了CCL 21诱导的OSCC细胞的EMT和干细胞性。当用CCL 21处理时，磷酸化JAK 2和磷酸化STAT 3显著增加。JAK 2/STAT 3抑制剂能显著抑制CCL 21诱导的OSCC细胞的EMT和干性。结论：CCL 21/CCR 7轴通过激活JAK 2/STAT 3信号通路调控EMT进程，促进OSCC的干性。CCL 21/CCR 7可能是口腔鳞癌防治的有效靶点。
Chemokines and their receptors show a strong relationship with poor clinical outcomes in various cancers. However, their underlying mechanisms remain to be fully elucidated. In our research, we found C-C chemokine receptor 7 (CCR7) and its ligand chemokine ligand 21 (CCL21) were abnormally abundant in oral squamous cell carcinoma (OSCC) tissues, and CCR7 expression was correlated with poor prognosis of OSCC. After exogenous CCL21 stimulation, epithelial-mesenchymal transition (EMT) was promoted in OSCC cells, and cancer stem cell-related markers CD133, CD44, BMI1, ALDH1A1, and OCT4 increased. The migration, invasion, tumorsphere formation, and colony formation abilities of OSCC cells were enhanced, indicating that the stemness of OSCC cells was also improved. The knockdown and overexpression of CCR7 efficiently affected the CCL21-induced EMT and stemness of OSCC cells. When treated with CCL21, the phospho-JAK2 and phospho-STAT3 markedly increased. The inhibitor of the Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) significantly suppressed CCL21-induced EMT and stemness of OSCC cells. In conclusion, CCL21/CCR7 axis regulated EMT progress and promoted the stemness of OSCC by activating the JAK2/STAT3 signaling pathway. CCL21/CCR7 might be an effective target for OSCC prevention and treatment.