Jak3 is involved in CCR7-dependent migration and invasion in metastatic squamous cellcarcinoma of the head and neck

【作者】 张忠提； 孙长伏；

【机构】 中国医科大学附属口腔医院；

【摘要】 Patients with cervical lymph node metastasis in squamous cell carcinoma of the head and neck(SCCHN) exhibit a poor prognosis and low 5-year survival rate. It has been proven that chemokine receptor 7(CCR7) promotes cellular migration and invasion in metastaticSCCHN. In the present study, the metastatic SCCHN PCI-37 B cell line was utilized to explore the role of Janus activated kinase-3(Jak3) in the CCR7-mediated signaling pathway in metastatic SCCHN cells. It was observed that phospho-Jak3 was expressed in SCCHN tissues. In addition, when the PCI-37 B cells were analyzed in response to chemokine ligand 19(CCL19), the ligand of CCR7, at the indicated time points, the results of the present study demonstrated that CCR7 induced Jak3 activation, and inhibition of Jak3 activity using a specific inhibitor, ZM39923, significantlyattenuateCCR7-induced Jak3 phosphorylation. Migration and invasion assays and immunofluorescence staining experiments demonstrated that CCL19 promoted cell migration, invasion and F-actin rearrangment in CCR7-expressing SCCHN cells partially due to the activation of the Jak3 signaling pathway. These results demonstrate that the Jak3 signaling pathway is important for the CCR7-induced malignant biological behavior of SCCHN cells.更多还原

【Abstract】 Patients with cervical lymph node metastasis in squamous cell carcinoma of the head and neck(SCCHN) exhibit a poor prognosis and low 5-year survival rate. It has been proven that chemokine receptor 7(CCR7) promotes cellular migration and invasion in metastaticSCCHN. In the present study, the metastatic SCCHN PCI-37 B cell line was utilized to explore the role of Janus activated kinase-3(Jak3) in the CCR7-mediated signaling pathway in metastatic SCCHN cells. It was observed that phospho-Jak3 was expressed in SCCHN tissues. In addition, when the PCI-37 B cells were analyzed in response to chemokine ligand 19(CCL19), the ligand of CCR7, at the indicated time points, the results of the present study demonstrated that CCR7 induced Jak3 activation, and inhibition of Jak3 activity using a specific inhibitor, ZM39923, significantlyattenuateCCR7-induced Jak3 phosphorylation. Migration and invasion assays and immunofluorescence staining experiments demonstrated that CCL19 promoted cell migration, invasion and F-actin rearrangment in CCR7-expressing SCCHN cells partially due to the activation of the Jak3 signaling pathway. These results demonstrate that the Jak3 signaling pathway is important for the CCR7-induced malignant biological behavior of SCCHN cells.更多还原