期刊
ONCOLOGY REPORTS
卷 25, 期 2, 页码 383-391出版社
SPANDIDOS PUBL LTD
DOI: 10.3892/or.2010.1090
关键词
NF-kappa B; CCR7; PI3K; squamous cell carcinoma of head and neck; survival
类别
资金
- National Natural Science Foundation of China [30672331]
- Foundation of Liaoning Educational Commission [2009A755]
Metastatic squamous cell carcinoma of the head and neck (SCCHN) has been shown to express chemokine receptor 7 (CCR7), which activates phosphoinositide-3 kinase/Akt/mammalian target of rapamycin (PI3K/Akt/mTOR) signal pathway to promote the invasion and survival of SCCHN cells. Since nuclear factor-kappa B (NF-kappa B) is shown to be the downstream signal molecule of PI3K/Akt in many tumors, we investigated whether it also exists in the CCR7 pathway in SCCHN, and the relationship between NF-kappa B and PI3K/Akt/mTOR, and the role it plays in SCCHN. We assayed the phosphorylation of the inhibitor of NF-kappa B (I kappa B alpha), the NF-kappa B DNA-binding capacity and location. The results showed that the interaction between CCR7 and the ligand for CCR7, CCL19, induces phosphorylation of I kappa B alpha, causes NF-kappa B to translocate to the nucleus and raises the DNA-binding capacity of NF-kappa B. The phosphorylation and DNA-binding capacity were abolished by the inhibition of CCR7, PI3K, Akt and mTOR. Further research demonstrated that inhibitors of NF-kappa B and CCR7-PI3K attenuate the survival of CCR7-mediated cells, causing decreased viability, increased apoptosis and increased cell cycle arrest in SCCHN cells. In clinical samples from 78 patients, immunohistochemical assay also showed that CCR7 and NF-kappa B are not only highly expressed in SCCHN, but also correlated with each other, and related to lymph node metastasis and clinical stage. Together, our data indicate that NF-kappa B is activated by CCR7 via PI3K/Akt/mTOR, and this signal pathway plays an important role in regulating the cell survival and prognosis of SCCHN.
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