PDF(Pubmed)
Abstract：
Human oral squamous cell carcinoma (OSCC) has been associated with a relatively low survival rate over the years and is characterized by a poor prognosis. C-X3-C motif chemokine ligand 1 (CX3CL1) has been involved in advanced migratory cells. Overexpressed CX3CL1 promotes several cellular responses related to cancer metastasis, including cell movement, migration and invasion in tumour cells. However, CX3CL1 controls the migration ability, and its molecular mechanism in OSCC remains unknown. The present study confirmed that CX3CL1 increased cell movement, migration and invasion. The CX3CL1-induced cell motility is upregulated through intercellular adhesion molecule-1 (ICAM-1) expression in OSCC cells. These effects were significantly suppressed when OSCC cells were pre-treated with CX3CR1 monoclonal antibody (mAb) and small-interfering RNA (siRNA). The CX3CL1-CX3CR1 axis activates promoted PLCβ/PKCα/c-Src phosphorylation. Furthermore, CX3CL1 enhanced activator protein-1 (AP-1) activity. The CX3CR1 mAb and PLCβ, PKCα, c-Src inhibitors reduced CX3CL1-induced c-Jun phosphorylation, c-Jun translocation into the nucleus and c-Jun binding to the ICAM-1 promoter. The present results reveal that CX3CL1 induces the migration of OSCC cells by promoting ICAM-1 expression through the CX3CR1 and the PLCβ/PKCα/c-Src signal pathway, suggesting that CX3CL1-CX3CR1-mediated signalling is correlated with tumour motility and appealed to be a precursor for prognosis in human OSCC.
摘要：
多年来，人类口腔鳞状细胞癌（OSCC）的生存率相对较低，并且预后不良。C-X3-C基序趋化因子配体1(CX3CL1)已介入晚期迁徙细胞。过度表达的CX3CL1促进与癌症转移相关的几种细胞反应，包括细胞运动，肿瘤细胞的迁移和侵袭。然而,CX3CL1控制迁移能力，其在OSCC中的分子机制尚不清楚。本研究证实CX3CL1增加了细胞运动，移民和入侵。CX3CL1诱导的细胞运动性通过OSCC细胞中的细胞间粘附分子-1(ICAM-1)表达上调。当用CX3CR1单克隆抗体(mAb)和小干扰RNA(siRNA)预处理OSCC细胞时,这些作用被显著抑制。CX3CL1-CX3CR1轴激活促进的PLCβ/PKCα/c-Src磷酸化。此外，CX3CL1增强激活蛋白-1(AP-1)活性。CX3CR1单克隆抗体和PLCβ，PKCα,c-Src抑制剂减少CX3CL1诱导的c-Jun磷酸化，c-Jun易位到细胞核和c-Jun结合到ICAM-1启动子。结果表明,CX3CL1通过CX3CR1和PLCβ/PKCα/c-Src信号通路促进ICAM-1表达,从而诱导OSCC细胞迁移,提示CX3CL1-CX3CR1介导的信号传导与肿瘤运动相关，并呼吁成为人类OSCC预后的前兆。
