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Identification of a novel therapeutic target for head and neck squamous cell carcinomas: A role for the neurotensin‐neurotensin receptor 1 oncogenic signaling pathway
Author(s) -
Shimizu Satoya,
Tsukada Jun,
Sugimoto Takashi,
Kikkawa Naoko,
Sasaki Keita,
Chazono Hideaki,
Hanazawa Toyoyuki,
Okamoto Yoshitaka,
Seki Naohiko
Publication year - 2008
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.23710
Subject(s) - cancer research , neurotensin , head and neck squamous cell carcinoma , biology , metastasis , neurotensin receptor , cancer , signal transduction , receptor , head and neck cancer , microbiology and biotechnology , neuropeptide , biochemistry , genetics
Distant metastasis is a major factor associated with poor prognosis in head and neck squamous cell carcinomas (HNSCC), but little is known of its molecular mechanisms. New markers that predict clinical outcome, in particular the ability of primary tumors to develop metastatic tumors, are urgently needed. Based on a genome‐wide gene expression analysis using clinical specimens of HNSCC, we narrowed our focus to the analysis of the neurotensin (NTS) and neurotensin receptor 1 (NTSR1) oncogenic signal pathways. Kaplan‐Meier curves and log rank tests revealed that high mRNA expression levels of NTS and NTSR1 had a significant adverse effect on metastasis‐free survival rate, suggesting a contribution of this pathway in HNSCC cancer progression. In HNSCC cells, which expressed NTSR1, a NTS agonist promoted cellular invasion, migration and induction of several mRNAs, such as interleukin 8 and matrix metalloproteinase 1 transcripts. In addition, knock down of NTSR1 expression with small interfering RNAs resulted in reduction of cellular invasion and migration in HNSCC cell lines. Our findings suggest a critical role for the NTS and NTSR1 oncogenic pathways in invasion and migration of HNSCC cells during the metastatic process. Our study raises the possibility that NTS and NTSR1 could be a useful predictive marker of poor prognosis in patients with HNSCC and a molecular therapeutic target in antimetastatic strategies for HNSCCs. © 2008 Wiley‐Liss, Inc.