title: CCR7 regulates cell migration and invasion through MAPKs in metastatic squamous cell carcinoma of head and neck.
abstract: Migration and invasion of tumor cells are essential prerequisites for the formation of metastasis in malignant diseases. Previously, we have reported that CC chemokine receptor 7 (CCR7) regulates the mobility of squamous cell carcinoma of head and neck (SCCHN) cells through several pathways, such as integrin and cdc42. In this study, we investigated the connection between CCR7 and mitogen-activated protein kinase (MAPK) family members, and their influence on cell invasion and migration in metastatic SCCHN cells. Western blotting, immunostaining and fluorescence microcopy were used to detect the protein expression and distribution of MAPKs, and the Migration assay, Matrigel invasion assay and wound-healing assay to detect the role of MAPKs in CCR7 regulating cell mobility. To analyze the correlation between CCR7 and MAPK activity and clinicopathological factors immunohistochemical staining was emplyed. The results showed stimulation of CCL19 and the activation of CCR7 could induce ERK1/2 and JNK phosphorylation, while it had no efect on p38. After activation, ERK1/2 and JNK promoted E-cadherin low expression and Vimentin high expression. The MAPK pathway not only mediated CCR7 induced cell migration, but also mediated invasion speed. The immunohistochemistry results showed that CCR7 was correlated with the phosphorylation of ERK1/2 and JNK in SCCHN, and these molecules were all associated with lymph node metastasis. Therefore, our study demonstrates that MAPK members (ERK1/2 and JNK) play a key role in CCR7 regulating SCCHN metastasis.
authors.affiliation: Departments of Oromaxillofacial ‑ Head and Neck Surgery and Oral and Maxillofacial Surgery, School of Stomatology, China Medical University, Shenyang, Liaoning 110002, P.R. China.
authors.forename: Fa-Yu
authors.initials: FY
authors.lastname: Liu
authors.affiliation: Departments of Oromaxillofacial ‑ Head and Neck Surgery and Oral and Maxillofacial Surgery, School of Stomatology, China Medical University, Shenyang, Liaoning 110002, P.R. China.
authors.forename: Jawad
authors.initials: J
authors.lastname: Safdar
authors.affiliation: Departments of Oromaxillofacial ‑ Head and Neck Surgery and Oral and Maxillofacial Surgery, School of Stomatology, China Medical University, Shenyang, Liaoning 110002, P.R. China.
authors.forename: Zhen-Ning
authors.initials: ZN
authors.lastname: Li
authors.affiliation: Departments of Oromaxillofacial ‑ Head and Neck Surgery and Oral and Maxillofacial Surgery, School of Stomatology, China Medical University, Shenyang, Liaoning 110002, P.R. China.
authors.forename: Qi-Gen
authors.initials: QG
authors.lastname: Fang
authors.affiliation: Departments of Oromaxillofacial ‑ Head and Neck Surgery and Oral and Maxillofacial Surgery, School of Stomatology, China Medical University, Shenyang, Liaoning 110002, P.R. China.
authors.forename: Xu
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Departments of Oromaxillofacial ‑ Head and Neck Surgery and Oral and Maxillofacial Surgery, School of Stomatology, China Medical University, Shenyang, Liaoning 110002, P.R. China.
authors.forename: Zhong-Fei
authors.initials: ZF
authors.lastname: Xu
authors.affiliation: Departments of Oromaxillofacial ‑ Head and Neck Surgery and Oral and Maxillofacial Surgery, School of Stomatology, China Medical University, Shenyang, Liaoning 110002, P.R. China.
authors.forename: Chang-Fu
authors.initials: CF
authors.lastname: Sun
mesh_terms: D000328:Adult; D000368:Aged; D015820:Cadherins / Q000096:biosynthesis; D002294:Carcinoma, Squamous Cell / Q000235:genetics*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics*; D054415:Chemokine CCL19 / Q000096:biosynthesis; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006258:Head and Neck Neoplasms / Q000235:genetics*; D006801:Humans; D008207:Lymphatic Metastasis / Q000235:genetics / Q000473:pathology; D048670:MAP Kinase Kinase 4 / Q000235:genetics*; D020935:MAP Kinase Signaling System / Q000235:genetics; D008297:Male; D008875:Middle Aged; D048052:Mitogen-Activated Protein Kinase 3 / Q000096:biosynthesis*; D054400:Receptors, CCR7 / Q000096:biosynthesis / Q000235:genetics*; D015398:Signal Transduction; D000077195:Squamous Cell Carcinoma of Head and Neck
chemical_list: C515370:CCR7 protein, human; D015820:Cadherins; D054415:Chemokine CCL19; D054400:Receptors, CCR7; D048052:Mitogen-Activated Protein Kinase 3; D048670:MAP Kinase Kinase 4