The State Key Laboratory Breeding Base of Basic Science of Stomatology, School and Hospital of Stomatology, Hubei Province & Key Laboratory of Oral Biomedicine (Wuhan University), Wuhan, China.
Department of Oral and Maxillofacial Head and Neck Oncology, School and Hospital of Stomatology, Wuhan University, Wuhan, China.
J Cell Physiol. 2020 Sep;235(9):5995-6009. doi: 10.1002/jcp.29525. Epub 2020 Feb 4.
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.
趋化因子及其受体与多种癌症的不良临床结局密切相关。然而，其潜在机制仍有待充分阐明。在我们的研究中，我们发现 C-C 趋化因子受体 7（CCR7）及其配体趋化因子配体 21（CCL21）在口腔鳞状细胞癌（OSCC）组织中异常丰富，CCR7 表达与 OSCC 的不良预后相关。外源性 CCL21 刺激后，OSCC 细胞中促进上皮-间充质转化（EMT），且癌症干细胞相关标志物 CD133、CD44、BMI1、ALDH1A1 和 OCT4 增加。OSCC 细胞的迁移、侵袭、肿瘤球形成和集落形成能力增强，表明 OSCC 细胞的干性也得到了提高。CCR7 的敲低和过表达可有效影响 CCL21 诱导的 OSCC 细胞 EMT 和干性。用 CCL21 处理后，磷酸化-JAK2 和磷酸化-STAT3 明显增加。Janus 激酶 2/信号转导和转录激活因子 3（JAK2/STAT3）抑制剂显著抑制 CCL21 诱导的 OSCC 细胞 EMT 和干性。总之，CCL21/CCR7 轴通过激活 JAK2/STAT3 信号通路调节 EMT 进展，并促进 OSCC 的干性。CCL21/CCR7 可能是预防和治疗 OSCC 的有效靶点。
