title: CC chemokine ligand 18(CCL18) promotes migration and invasion of lung cancer cells by binding to Nir1 through Nir1-ELMO1/DOC180 signaling pathway.
abstract: Non-small cell lung cancer (NSCLC) comprises nearly 80% of lung cancers and the poor prognosis is due to its high invasiveness and metastasis. CC chemokine ligand 18 (CCL18) is predominantly secreted by M2-tumor associated macrophages (TAMs) and promotes malignant behaviors of various human cancer types. In this study, we report that the high expression of CCL18 in TAMs of NSCLC tissues and increased expression of CCL18 in TAMs is correlated with the lymph node metastasis, distant metastasis, and poor prognosis NSCLC patients. CCL18 can increase the invasive ability of NSCLC cells by binding to its receptor Nir1. In addition, CCL18 is capable of modulating cell migration and invasion by regulating the activation of RAC1 which resulted in cytoskeleton reorganization in an ELMO1 dependent manner. Furthermore, we found that CCL18 could enhance adhesion of NSCLC cells via activating ELMO1-integrin β1 signaling. Thus, CCL18 and its downstream molecules may be used as targets to develop novel NSCLC therapy. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Department of Pharmacology, Weifang Medical University, Weifang, P. R. China.
authors.forename: Lihong
authors.initials: L
authors.lastname: Shi
authors.affiliation: Department of Pathology, Weifang Medical University, Weifang, P. R. China.
authors.forename: Baogang
authors.initials: B
authors.lastname: Zhang
authors.affiliation: Department of Microbilology, Weifang Medical University, Weifang, P. R. China.
authors.forename: Xiuning
authors.initials: X
authors.lastname: Sun
authors.affiliation: Department of Pharmacology, Weifang Medical University, Weifang, P. R. China.
authors.forename: Xiurong
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Pathology, Weifang Medical University, Weifang, P. R. China.
authors.forename: Shijun
authors.initials: S
authors.lastname: Lv
authors.affiliation: Department of Medicine Research Center, Weifang Medical University, Weifang, P. R. China.
authors.forename: Hongli
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Pharmacology, Weifang Medical University, Weifang, P. R. China.
authors.forename: Xuejian
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Pharmacology, Weifang Medical University, Weifang, P. R. China.
authors.forename: Chunzhen
authors.initials: C
authors.lastname: Zhao
authors.affiliation: Department of Pharmacology, Weifang Medical University, Weifang, P. R. China.
authors.forename: Heng
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Pharmacology, Weifang Medical University, Weifang, P. R. China.
authors.forename: Xinpeng
authors.initials: X
authors.lastname: Xie
authors.affiliation: Department of Pharmacology, Weifang Medical University, Weifang, P. R. China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Pharmacology, Weifang Medical University, Weifang, P. R. China.
authors.forename: Peng
authors.initials: P
authors.lastname: Zhang
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000032:analysis / Q000276:immunology*; D000818:Animals; D002135:Calcium-Binding Proteins / Q000032:analysis / Q000276:immunology*; D002289:Carcinoma, Non-Small-Cell Lung / Q000276:immunology / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement; D019742:Chemokines, CC / Q000032:analysis / Q000276:immunology*; D005260:Female; D006801:Humans; D008168:Lung / Q000473:pathology*; D008175:Lung Neoplasms / Q000276:immunology / Q000473:pathology*; D008207:Lymphatic Metastasis / Q000276:immunology / Q000473:pathology; D008297:Male; D008565:Membrane Proteins / Q000032:analysis / Q000276:immunology*; D051379:Mice; D016513:Mice, SCID; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000276:immunology / Q000473:pathology; D015398:Signal Transduction; D020744:rac GTP-Binding Proteins / Q000032:analysis / Q000276:immunology
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C111792:CCL18 protein, human; D002135:Calcium-Binding Proteins; D019742:Chemokines, CC; C099818:DOCK1 protein, human; C465214:ELMO1 protein, human; D008565:Membrane Proteins; C117885:PITPNM3 protein, human; D020744:rac GTP-Binding Proteins
keywords: CC chemokine ligand 18; ELMO1; Nir1; invasion; matastasis