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Chemokine receptor 7 activates phosphoinositide-3 kinase-mediated invasive and prosurvival pathways in head and neck cancer cells independent of EGFR
- Source :
- Oncogene. 24(38)
- Publication Year :
- 2005
-
Abstract
- Chemokine receptor 7 (CCR7) upregulation, which mediates immune cell survival and migration to lymph nodes, has recently been associated with nodal metastasis of squamous cell carcinoma of the head and neck (SCCHN). However, the mechanism of CCR7 in tumor progression, its downstream signaling mediators, and interactions with other pathways contributing to metastasis of SCCHN have not been determined. We hypothesized that inflammatory chemokine-mediated signals could also promote tumor proliferation and mitogenic effects. Functional assays showed that chemotaxis and invasion of metastatic SCCHN cells were dependent on phosphoinositide-3 kinase (PI3K) and its substrate, activated phospholipase Cgamma-1. In addition, treatment of CCR7(+) metastatic SCCHN cells with CCL19 (MIP-3beta) showed rapid activation of the prosurvival, PI3K/Akt pathway. Transactivation of EGFR-mediated and mitogen-activated protein kinase signaling pathways, which can promote migration and survival in parallel, did not appear to contribute to the functional or biochemical effects of CCR7 stimulation. Thus, proinflammatory chemokine signals that mediate activation, trafficking and survival of tumor-infiltrating immune cells in the tumor microenvironment actually appear to induce signals for progression of cancer cells. The CCR7-mediated pathway in metastatic SCCHN cells functions independently of EGFR signal transduction and therefore may represent an additional target for therapeutic intervention to prevent tumor progression and metastasis.
- Subjects :
- Cancer Research
Receptors, CCR7
Immunoblotting
C-C chemokine receptor type 7
medicine.disease_cause
Chemokine receptor
Cell Line, Tumor
Genetics
medicine
Humans
Immunoprecipitation
Neoplasm Invasiveness
Epidermal growth factor receptor
Molecular Biology
Protein kinase B
1-Phosphatidylinositol 4-Kinase
PI3K/AKT/mTOR pathway
Phosphoinositide 3-kinase
biology
Kinase
Phospholipase C gamma
Chemotaxis
Enzyme Activation
ErbB Receptors
Head and Neck Neoplasms
Type C Phospholipases
biology.protein
Cancer research
Receptors, Chemokine
Carcinogenesis
Subjects
Details
- ISSN :
- 09509232
- Volume :
- 24
- Issue :
- 38
- Database :
- OpenAIRE
- Journal :
- Oncogene
- Accession number :
- edsair.doi.dedup.....9ab0ed22986e3e6b9aa5d3c0fd14d8c9