CCL21/CCR7 interaction promotes EMT and enhances the stemness of OSCC via a JAK2/STAT3 signaling pathway. Issue 9 (4th February 2020)

• Record Type: Journal Article
• Authors: Chen, Yang; Shao, Zhe; Jiang, Erhui; Zhou, Xiaocheng; Wang, Lin; Wang, Hui; Luo, Xinyue; Chen, Qingli; Liu, Ke; Shang, Zhengjun
• Is Part Of: Journal of cellular physiology. Volume 235:Issue 9(2020:Sep.)
• Page Start: 5995
• Page End: 6009
• Publication Date: 2020-02-04
• Subjects: cancer stem cells -- chemokine -- EMT -- JAK2/STAT3 -- OSCC; Physiology -- Periodicals; Cell physiology -- Periodicals; 571.6
• DOI: 10.1002/jcp.29525
• Languages: English
• ISSNs: 0021-9541

Abstract

Abstract: 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. Abstract : Chemokine ligand 21/C‐C chemokine receptor 7 (CCL21/CCR7) axis regulates epithelial–mesenchymal transition progress and promotes the stemness of oral squamous cell carcinoma (OSCC) by activating the Janus kinase 2/signal transducer and activator of transcription 3 signaling pathway. CCL21/CCR7 might be an effective target for OSCC prevention and treatment.