title: High expression of Toll-like receptor 5 correlates with better prognosis in non-small-cell lung cancer: an anti-tumor effect of TLR5 signaling in non-small cell lung cancer.
abstract: OBJECTIVE
  Toll-like receptor 5 (TLR5) is a pattern recognition receptor and plays key roles in inflammatory responses against pathogen infection. Recent evidence suggests that TLR5 is expressed in a wide variety of tumors and exhibits either pro-tumor or anti-tumor activities. In this study, we explored expression of TLR5 in the context of non-small-cell lung cancer (NSCLC) and evaluated the effects of TLR5 signaling in NSCLC cells.
  
  
  METHODS
  The lung carcinoma samples were collected from 113 patients diagnosed as NSCLC at Tumor Hospital of Xiangya School of Medicine from January 2005 to December 2008. Immunohistochemistry was performed for TLR5 and the protein expression score was quantified using an established scoring system. Kaplan-Meier survival curves were generated for disease-free survival (DFS) and overall survival (OS) in all patients. TLR5 expression levels were correlated with DFS and OS using univariate and multivariate Cox regression analysis. Expression and subcellular localization of TLR5 were analyzed in NSCLC cell lines including SPC-A1, A549, H1975, and H1299 cells. Activation of TLR5 signaling pathway by flagellin was characterized by western blotting. Effects of flagellin on NSCLC cell proliferation, anchorage-independent growth, migration, and invasion were analyzed by BrdU incorporation assay, soft agar colony formation assay, wound-healing migration assay, and transwell invasion assay, respectively.
  
  
  RESULTS
  High expression of TLR5 was significantly associated with better prognosis in patients with NSCLC. We further demonstrated that activation of TLR5 by flagellin in NSCLC cells inhibited cell proliferation, migration, and invasion in vitro.
  
  
  CONCLUSIONS
  TLR5 may serve as a potential therapeutic target in NSCLC patients.
authors.affiliation: Department of Oncology, Xiangya Hospital, Central South University, Changsha, 410078, People's Republic of China.
authors.forename: Hui
authors.initials: H
authors.lastname: Zhou
authors.forename: Jian-hua
authors.initials: JH
authors.lastname: Chen
authors.forename: Jun
authors.initials: J
authors.lastname: Hu
authors.forename: Yong-zhong
authors.initials: YZ
authors.lastname: Luo
authors.forename: Fang
authors.initials: F
authors.lastname: Li
authors.forename: Ling
authors.initials: L
authors.lastname: Xiao
authors.forename: Mei-zuo
authors.initials: MZ
authors.lastname: Zhong
mesh_terms: D000230:Adenocarcinoma / Q000175:diagnosis / Q000378:metabolism / Q000473:pathology; D014408:Biomarkers, Tumor / Q000378:metabolism*; D015153:Blotting, Western; D002289:Carcinoma, Non-Small-Cell Lung / Q000175:diagnosis* / Q000378:metabolism* / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000175:diagnosis / Q000378:metabolism / Q000473:pathology; D002465:Cell Movement; D049109:Cell Proliferation; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007124:Immunoenzyme Techniques; D008156:Luciferases / Q000378:metabolism; D008175:Lung Neoplasms / Q000175:diagnosis / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D015996:Survival Rate; D051198:Toll-Like Receptor 5 / Q000378:metabolism*; D014945:Wound Healing
chemical_list: D014408:Biomarkers, Tumor; D012333:RNA, Messenger; C495346:TLR5 protein, human; D051198:Toll-Like Receptor 5; D008156:Luciferases