title: RANKL increases migration of human lung cancer cells through intercellular adhesion molecule-1 up-regulation.
abstract: Invasion of distant tissues by tumor cells is the primary cause of therapeutic failure in the treatment of malignant lung cancer cells. Receptor activator of nuclear factor-κB ligand (RANKL) and its receptor, RANK, play a key role in osteoclastogenesis and tumor metastasis. Intercellular adhesion molecule-1 (ICAM-1, also called CD54), a member of the immunoglobulin supergene family, is an inducible surface glycoprotein that mediates adhesion-dependent cell-to-cell interactions. The effects of RANKL on cell migration and ICAM-1 expression in human lung cancer cells are largely unknown. We found that RANKL directed the migration and increased ICAM-1 expression in human lung cancer (A549) cells. Pretreatment of A549 cells with the MAPK kinase (MEK) inhibitor PD98059 or U0126 inhibited RANKL-mediated migration and ICAM-1 expression. Stimulation of cells with RANKL increased the phosphorylation of MEK and extracellular signal-regulating kinase (ERK). In addition, an NF-κB inhibitor (PDTC) and IκB protease inhibitor (TPCK) also inhibited RANKL-mediated cell migration and ICAM-1 up-regulation. Taken together, these results suggest that the RANKL and RANK interaction acts through MEK/ERK, which in turn activates NF-κB, resulting in the activation of ICAM-1 and contributing to the migration of human lung cancer cells.
authors.affiliation: Center of General Education, Central Taiwan University of Science & Technology, Taichung, Taiwan.
authors.forename: Li-Mien
authors.initials: LM
authors.lastname: Chen
authors.forename: Chia-Hua
authors.initials: CH
authors.lastname: Kuo
authors.forename: Tung-Yuan
authors.initials: TY
authors.lastname: Lai
authors.forename: Yueh-Min
authors.initials: YM
authors.lastname: Lin
authors.forename: Cheng-Chuan
authors.initials: CC
authors.lastname: Su
authors.forename: His-Hsien
authors.initials: HH
authors.lastname: Hsu
authors.forename: Fuu-Jen
authors.initials: FJ
authors.lastname: Tsai
authors.forename: Chang-Hai
authors.initials: CH
authors.lastname: Tsai
authors.forename: Chih-Yang
authors.initials: CY
authors.lastname: Huang
authors.forename: Chih-Hsin
authors.initials: CH
authors.lastname: Tang
mesh_terms: D045744:Cell Line, Tumor; D002465:Cell Movement; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D017930:Genes, Reporter; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis* / Q000235:genetics; D008156:Luciferases / Q000378:metabolism; D008175:Lung Neoplasms / Q000378:metabolism / Q000473:pathology*; D048369:MAP Kinase Kinase 1 / Q000378:metabolism; D048370:MAP Kinase Kinase 2 / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D010766:Phosphorylation; D053245:RANK Ligand / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D034622:RNA Interference; D015398:Signal Transduction; D015854:Up-Regulation
chemical_list: D016328:NF-kappa B; D053245:RANK Ligand; C505688:TNFSF11 protein, human; D018799:Intercellular Adhesion Molecule-1; D008156:Luciferases; C482128:MAP2K2 protein, human; D048049:Extracellular Signal-Regulated MAP Kinases; D048369:MAP Kinase Kinase 1; D048370:MAP Kinase Kinase 2; C482125:MAP2K1 protein, human