Document Detail


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.
MedLine Citation:
PMID:  19615795     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Fa-Yu Liu; Zhen-Jin Zhao; Peng Li; Xue Ding; Zhi-Hong Zong; Chang-Fu Sun
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-07-16
Journal Detail:
Title:  The British journal of oral & maxillofacial surgery     Volume:  48     ISSN:  1532-1940     ISO Abbreviation:  Br J Oral Maxillofac Surg     Publication Date:  2010 Jun 
Date Detail:
Created Date:  2010-05-17     Completed Date:  2010-08-18     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8405235     Medline TA:  Br J Oral Maxillofac Surg     Country:  Scotland    
Other Details:
Languages:  eng     Pagination:  291-6     Citation Subset:  D; IM    
Copyright Information:
Copyright 2009 The British Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.
Affiliation:
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.
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MeSH Terms
Descriptor/Qualifier:
1-Phosphatidylinositol 3-Kinase / antagonists & inhibitors,  physiology*
Antibodies, Monoclonal / diagnostic use
Antineoplastic Agents / pharmacology
Apoptosis / drug effects
Blotting, Western
Carcinoma, Squamous Cell / pathology,  secondary*
Cell Cycle / drug effects
Cell Death / drug effects
Cell Line, Tumor
Cell Survival / drug effects,  physiology
Chemokine CCL19 / physiology
Chromones / pharmacology
Cisplatin / pharmacology
Coloring Agents / diagnostic use
Enzyme Inhibitors / pharmacology
Flow Cytometry
Head and Neck Neoplasms / pathology,  secondary*
Humans
Intracellular Signaling Peptides and Proteins / antagonists & inhibitors,  physiology*
Morpholines / pharmacology
Neoplasm Invasiveness
Phosphorylation
Polymerase Chain Reaction / methods
Protein-Serine-Threonine Kinases / antagonists & inhibitors,  physiology*
Proto-Oncogene Proteins c-akt / antagonists & inhibitors,  physiology*
Receptors, CCR7 / antagonists & inhibitors,  physiology*
Ribosomal Protein S6 Kinases, 70-kDa / physiology
Sirolimus / pharmacology
Tetrazolium Salts / diagnostic use
Thiazoles / diagnostic use
Chemical
Reg. No./Substance:
0/Antibodies, Monoclonal; 0/Antineoplastic Agents; 0/CCL19 protein, human; 0/CCR7 protein, human; 0/Chemokine CCL19; 0/Chromones; 0/Coloring Agents; 0/Enzyme Inhibitors; 0/Intracellular Signaling Peptides and Proteins; 0/Morpholines; 0/Receptors, CCR7; 0/Tetrazolium Salts; 0/Thiazoles; 154447-36-6/2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; 15663-27-1/Cisplatin; 298-93-1/thiazolyl blue; 53123-88-9/Sirolimus; EC 2.7.1.-/mTOR protein; EC 2.7.1.137/1-Phosphatidylinositol 3-Kinase; EC 2.7.11.1/Protein-Serine-Threonine Kinases; EC 2.7.11.1/Proto-Oncogene Proteins c-akt; EC 2.7.11.1/Ribosomal Protein S6 Kinases, 70-kDa

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