SDF-1α promotes invasion of head and neck squamous cell carcinoma by activating NF-κB
SDF-1α promotes invasion of head and neck squamous cell carcinoma by activating NF-κB
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DOI：
10.1074/jbc.m710432200
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发表时间：
2008-07-18
影响因子：
4.8
通讯作者：
Wang, Cun-Yu
中科院分区：
文献类型：
--
作者：
Rehman, Aasia O.;Wang, Cun-Yu
CXCL 12/基质细胞衍生因子-1 α（SDF-1 α）是G蛋白偶联受体CXCR 4的趋化因子配体，在细胞定向运动中起重要作用。许多研究已经证明了CXCR 4在肿瘤进展和器官特异性转移中的重要性。最近，一些研究已经暗示了SDF-1 α在头颈部鳞状细胞癌（HNSCC）转移中的作用，但目前关于SDF-1 α如何促进HNSCC转移的信息很少。在这份报告中，我们表明，NF-κ B信号通路被激活，以响应SDF-1 α在HNSCC，而原代和永生化角质形成细胞显示没有SDF-1 α介导的NF-κ B活性。我们发现SDF-1 α介导的NF-κ B信号通路不依赖于磷酸肌醇3-激酶/Akt和ERK/MAPK通路。我们观察到SDF-1 α诱导HNSCC细胞系中I κ B α磷酸化和降解以及NF-κ B的核转位，表明SDF-1 α激活经典的NF-κ B信号通路。与以前的报道相反，SDF-1 α诱导的NF-κ B活化不是由肿瘤坏死因子α介导的。此外，用IKK β抑制剂阻断NF-κ B信号通路显著降低了SDF-1 α介导的HNSCC侵袭。综上所述，我们的数据表明SDF-1 α/CXCR 4可能通过激活NF-κ B促进HNSCC侵袭和转移，靶向NF-κ B可能为预防SDF-1 α介导的HNSCC转移提供治疗机会。
CXCL12/stromal cell-derived factor-1 alpha (SDF-1 alpha), a chemokine ligand for the G protein-coupled receptor CXCR4, plays an important role in the directed movement of cells. Many studies have documented the importance of CXCR4 in tumor progression and organ-specific metastasis. Recently, several studies have implicated a role for SDF-1 alpha in head and neck squamous cell carcinoma (HNSCC) metastasis, but currently there is little information about how SDF-1 alpha promotes HNSCC metastasis. In this report we show that the NF-kappa B signaling pathway is activated in response to SDF-1 alpha in HNSCC while primary and immortalized keratinocytes show no SDF-1 alpha-mediated NF-kappa B activity. We found that SDF-1 alpha-mediated NF-kappa B signaling is independent of phosphoinositide 3-kinase/Akt and ERK/MAPK pathways. We observed that SDF-1 alpha induces I kappa B alpha phosphorylation and degradation and the nuclear translocation of NF-kappa B in HNSCC cell lines, suggesting that SDF-1 alpha activates the classical NF-kappa B signaling pathway. Contrary to previous reports, SDF-1 alpha-induced NF-kappa B activation is not mediated by tumor necrosis factor alpha. Furthermore, blocking the NF-kappa B signaling pathway with an IKK beta inhibitor significantly reduces SDF-1 alpha-mediated HNSCC invasion. Taken together, our data suggest SDF-1 alpha/CXCR4 may promote HNSCC invasion and metastasis by activating NF-kappa B and that targeting NF-kappa B may provide therapeutic opportunities in preventing HNSCC metastasis mediated by SDF-1 alpha.