NF-κB participates in chemokine receptor 7-mediated cell survival in metastatic squamous cell carcinoma of the head and neck

  • Authors:
    • Fa-Yu Liu
    • Zhen-Jin Zhao
    • Peng Li
    • Xue Ding
    • Nan Guo
    • Liang-Liang Yang
    • Zhi-Hong Zong
    • Chang-Fu Sun
  • View Affiliations

  • Published online on: December 9, 2010     https://doi.org/10.3892/or.2010.1090
  • Pages: 383-391
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Abstract

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-κB) 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-κB and PI3K/Akt/mTOR, and the role it plays in SCCHN. We assayed the phosphorylation of the inhibitor of NF-κB (IκBα), the NF-κB DNA-binding capacity and location. The results showed that the interaction between CCR7 and the ligand for CCR7, CCL19, induces phosphorylation of IκBα, causes NF-κB to translocate to the nucleus and raises the DNA-binding capacity of NF-κB. The phosphorylation and DNA-binding capacity were abolished by the inhibition of CCR7, PI3K, Akt and mTOR. Further research demonstrated that inhibitors of NF-κB 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-κB 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-κB 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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February 2011
Volume 25 Issue 2

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Spandidos Publications style
Liu F, Zhao Z, Li P, Ding X, Guo N, Yang L, Zong Z and Sun C: NF-κB participates in chemokine receptor 7-mediated cell survival in metastatic squamous cell carcinoma of the head and neck. Oncol Rep 25: 383-391, 2011
APA
Liu, F., Zhao, Z., Li, P., Ding, X., Guo, N., Yang, L. ... Sun, C. (2011). NF-κB participates in chemokine receptor 7-mediated cell survival in metastatic squamous cell carcinoma of the head and neck. Oncology Reports, 25, 383-391. https://doi.org/10.3892/or.2010.1090
MLA
Liu, F., Zhao, Z., Li, P., Ding, X., Guo, N., Yang, L., Zong, Z., Sun, C."NF-κB participates in chemokine receptor 7-mediated cell survival in metastatic squamous cell carcinoma of the head and neck". Oncology Reports 25.2 (2011): 383-391.
Chicago
Liu, F., Zhao, Z., Li, P., Ding, X., Guo, N., Yang, L., Zong, Z., Sun, C."NF-κB participates in chemokine receptor 7-mediated cell survival in metastatic squamous cell carcinoma of the head and neck". Oncology Reports 25, no. 2 (2011): 383-391. https://doi.org/10.3892/or.2010.1090