Mammalian target of rapamycin (mTOR) is involved in the survival of cells mediated by chemokine receptor 7 through PI3K/Akt in metastatic squamous cell carcinoma of the head and neck.
Metastatic squamous cell carcinoma (SCC) of the head and neck expresses chemokine receptor 7 (CCR7), which activates phosphoinositide-3 kinase (PI3K) to promote invasion and survival of SCC cells in the head and neck. We hypothesised that mammalian target of rapamycin (mTOR) may be the downstream molecule of the CCR7-PI3K pathway. Results have shown that interaction between CCR7 and its ligand CCL19 induces the phosphorylation of mTOR and its target p70s6k. This phosphorylation is abolished by inhibition of CCR7 and PI3K/Akt, indicating that mTOR is involved in the CCR7-PI3K cascade. The inhibitors of mTOR and CCR7-PI3K also lead to a significant increase in CCL19-induced death, apoptosis, and cell-cycle arrest of metastatic SCC cells in the head and neck. Taken together, our data indicate the important part played by mTOR in CCR7-induced survival of such SCC cells.
Liu
Fa-Yu
FY
Oral and Maxillofacial Tumor Center, Department of Oral and Maxillofacial Surgery, School of Stomatology, China Medical University, No. 117, Nanjing Bei Jie, Heping District, Shenyang, Liaoning 110002, China.
Zhao
Zhen-Jin
ZJ
Li
Peng
P
Ding
Xue
X
Zong
Zhi-Hong
ZH
Sun
Chang-Fu
CF
D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000473:pathology / Q000556:secondary*; D002453:Cell Cycle / Q000187:drug effects; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D054415:Chemokine CCL19 / Q000502:physiology; D002867:Chromones / Q000494:pharmacology; D002945:Cisplatin / Q000494:pharmacology; D004396:Coloring Agents; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005434:Flow Cytometry; D006258:Head and Neck Neoplasms / Q000473:pathology / Q000556:secondary*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000037:antagonists & inhibitors / Q000502:physiology*; D009025:Morpholines / Q000494:pharmacology; D009361:Neoplasm Invasiveness; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010766:Phosphorylation; D016133:Polymerase Chain Reaction / Q000379:methods; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000502:physiology*; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors / Q000502:physiology*; D054400:Receptors, CCR7 / Q000037:antagonists & inhibitors / Q000502:physiology*; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000502:physiology; D020123:Sirolimus / Q000494:pharmacology; D058570:TOR Serine-Threonine Kinases; D013778:Tetrazolium Salts; D013844:Thiazoles
D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D054415:Chemokine CCL19; D002867:Chromones; D002945:Cisplatin; D004396:Coloring Agents; D004791:Enzyme Inhibitors; D047908:Intracellular Signaling Peptides and Proteins; D009025:Morpholines; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; D054400:Receptors, CCR7; D038762:Ribosomal Protein S6 Kinases, 70-kDa; D020123:Sirolimus; D058570:TOR Serine-Threonine Kinases; D013778:Tetrazolium Salts; D013844:Thiazoles; C515460:CCL19 protein, human; C515370:CCR7 protein, human; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; C546842:MTOR protein, human; C022616:thiazolyl blue