title: Visfatin Triggers the Cell Motility of Non-Small Cell Lung Cancer via Up-Regulation of Matrix Metalloproteinases.
abstract: High levels of visfatin are correlated with worse clinical prognosis of various cancers. Still, the effects and mechanisms of visfatin on progression of non-small cell lung cancer (NSCLC) remain unclear. This study revealed that plasma levels of visfatin in patients with NSCLC (585 ± 287 pg/ml) were significantly (p < 0.01) higher than those in healthy people (142 ± 61.1 pg/ml). The high level of plasma visfatin was found to be significantly (p < 0.05) correlated with TNM stage, lymph node metastasis and distant metastasis. Visfatin treatment can increase the migration and invasion of NSCLC cells via up-regulation of metalloproteinase-2 (MMP-2) and MMP-9. Both si-MMP-2 and si-MMP-9 attenuated visfatin-induced migration of NSCLC cells. The inhibitor of NF-κB, while not ERK1/2, p38-MAPK or PI3K/Akt, can significantly abolish visfatin-induced migration of A549 cells and up-regulation of MMP-2 and MMP-9. Furthermore, visfatin can increase the phosphorylation of IκBα and p65 and the transcription activities of NF-κB in NSCLC cells. ACHP, the inhibitor of IKK-β, blocked visfatin-induced activation of p65 and up-regulation of MMP-2 and MMP-9. Collectively, our data revealed that visfatin can trigger the in vitro migration and invasion of NSCLC cells via up-regulation of MMPs through activation of NF-κB.
authors.affiliation: Department of Respiratory Medicine, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan, Shandong, China.
authors.forename: Guanghai
authors.initials: G
authors.lastname: Wang
authors.affiliation: Department of Clinical Laboratory, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong, China.
authors.forename: Wenjun
authors.initials: W
authors.lastname: Tian
authors.affiliation: Department of Clinical Laboratory, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong, China.
authors.forename: Yiqing
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Clinical Laboratory, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Ju
authors.affiliation: Department of Clinical Laboratory, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong, China.
authors.forename: Yajuan
authors.initials: Y
authors.lastname: Shen
authors.affiliation: Department of Clinical Laboratory, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong, China.
authors.forename: Shengmei
authors.initials: S
authors.lastname: Zhao
authors.affiliation: Department of Clinical Laboratory, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong, China.
authors.forename: Bingchang
authors.initials: B
authors.lastname: Zhang
authors.affiliation: Department of Respiratory Medicine, Qilu Hospital, Shandong University, Jinan, Shandong, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Li
mesh_terms: D000368:Aged; D002289:Carcinoma, Non-Small-Cell Lung / Q000097:blood* / Q000378:metabolism / Q000473:pathology / Q000556:secondary; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D016207:Cytokines / Q000097:blood* / Q000378:metabolism; D004790:Enzyme Induction; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000097:blood* / Q000378:metabolism / Q000473:pathology; D008207:Lymphatic Metastasis; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D000072000:NF-KappaB Inhibitor alpha / Q000378:metabolism; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D054409:Nicotinamide Phosphoribosyltransferase / Q000097:blood* / Q000378:metabolism; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D034622:RNA Interference; D015854:Up-Regulation
chemical_list: D016207:Cytokines; D000072000:NF-KappaB Inhibitor alpha; D054409:Nicotinamide Phosphoribosyltransferase; C085455:nicotinamide phosphoribosyltransferase, human; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9