title: Activation of FGF receptor signaling promotes invasion of non-small-cell lung cancer.
abstract: The molecular regulation of metastasis of non-small-cell lung cancer (NSCLC) remains not completely defined. Here we showed significant higher MMP26 in the resected NSCLC than adjacent healthy tissue from the patients. Moreover, a strong correlation between MMP26 and the phosphorylated fibroblast growth factor receptor 1 (FGFR1) was detected. To examine the causal relationship between activated FGFR signaling and MMP26, we studied a human NSCLC cell line, A549. We found that FGF1-induced FGFR1 phosphorylation in A549 cells activated MMP26, resulting in an increase in cancer invasiveness. Inhibition of FGFR1 phosphorylation abolished FGF1-stimulated MMP26 activation, suggesting that activation of FGFR signaling pathway in NSCLC promotes cancer metastasis through MMP26. To define the signal transduction cascades downstream of FGFR1 activation for MMP26 activation, we used specific inhibitors for PI3K, ERK/MAPK, and JNK, respectively, to the FGF1-stimulated A549 cells. We found that only inhibition of JNK significantly decreased the activation of MMP26 in response to FGF1 stimulation, suggesting that activation of FGFR1 signaling may activate JNK to activate MMP26 in NSCLC. Our study thus highlights FGFR signaling pathway and MMP26 as novel therapeutic targets for NSCLC therapy.
authors.affiliation: Department of Thoracic Surgery, Changzheng Hospital, Second Military Medical University, 415 Fengyang Road, Shanghai, 200433, China, deping_zhao14@163.com.
authors.forename: Deping
authors.initials: D
authors.lastname: Zhao
authors.forename: Yi
authors.initials: Y
authors.lastname: Lu
authors.forename: Chenlu
authors.initials: C
authors.lastname: Yang
authors.forename: Xiao
authors.initials: X
authors.lastname: Zhou
authors.forename: Zhifei
authors.initials: Z
authors.lastname: Xu
mesh_terms: D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D016220:Fibroblast Growth Factor 1 / Q000008:administration & dosage / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D006801:Humans; D048670:MAP Kinase Kinase 4 / Q000037:antagonists & inhibitors; D053505:Matrix Metalloproteinases, Secreted / Q000096:biosynthesis* / Q000235:genetics; D009361:Neoplasm Invasiveness / Q000235:genetics; D009362:Neoplasm Metastasis; D010766:Phosphorylation; D051496:Receptor, Fibroblast Growth Factor, Type 1 / Q000096:biosynthesis* / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics
chemical_list: D016220:Fibroblast Growth Factor 1; C496348:FGFR1 protein, human; D051496:Receptor, Fibroblast Growth Factor, Type 1; D048670:MAP Kinase Kinase 4; C410599:MMP26 protein, human; D053505:Matrix Metalloproteinases, Secreted