title: NEDD9 promotes lung cancer metastasis through epithelial-mesenchymal transition.
abstract: Metastasis is the major cause for high mortality of lung cancer with the underlying mechanisms poorly understood. The scaffolding protein neural precursor cell expressed, developmentally down-regulated 9 (NEDD9) has been identified as a pro-metastasis gene in several types of cancers including melanoma and breast cancer. However, the exact role and related mechanism of NEDD9 in regulating lung cancer metastasis still remain largely unknown. Here, we demonstrate that NEDD9 knockdown significantly inhibits migration, invasion and metastasis of lung cancer cells in vitro and in vivo. The pro-metastasis role of Nedd9 in lung cancer is further supported by studies in mice models of spontaneous cancer metastasis. Moreover, we find that NEDD9 promotes lung cancer cell migration and invasion through the induction of epithelial-mesenchymal transition (EMT) potentially via focal adhesion kinase activation. More importantly, NEDD9 expression inversely correlates with E-cadherin expression in human lung cancer specimens, consistent with the findings from in vitro studies. Taken together, this study highlights that NEDD9 is an important mediator promotes lung cancer metastasis via EMT.
authors.affiliation: State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, People's Republic of China.
authors.forename: Yujuan
authors.initials: Y
authors.lastname: Jin
authors.forename: Fei
authors.initials: F
authors.lastname: Li
authors.forename: Chao
authors.initials: C
authors.lastname: Zheng
authors.forename: Ye
authors.initials: Y
authors.lastname: Wang
authors.forename: Zhaoyuan
authors.initials: Z
authors.lastname: Fang
authors.forename: Chenchen
authors.initials: C
authors.lastname: Guo
authors.forename: Xujun
authors.initials: X
authors.lastname: Wang
authors.forename: Hongyan
authors.initials: H
authors.lastname: Liu
authors.forename: Lei
authors.initials: L
authors.lastname: Deng
authors.forename: Cheng
authors.initials: C
authors.lastname: Li
authors.forename: Hongda
authors.initials: H
authors.lastname: Wang
authors.forename: Haiquan
authors.initials: H
authors.lastname: Chen
authors.forename: Yan
authors.initials: Y
authors.lastname: Feng
authors.forename: Hongbin
authors.initials: H
authors.lastname: Ji
mesh_terms: D055372:AMP-Activated Protein Kinases; D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western; D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics*; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D057809:HEK293 Cells; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D008819:Mice, Nude; D008822:Mice, Transgenic; D009362:Neoplasm Metastasis; D020411:Oligonucleotide Array Sequence Analysis; D010750:Phosphoproteins / Q000235:genetics* / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D059467:Transcriptome
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D015820:Cadherins; C099942:NEDD9 protein, human; D010750:Phosphoproteins; D051416:Focal Adhesion Protein-Tyrosine Kinases; D017346:Protein Serine-Threonine Kinases; C491654:Stk11 protein, mouse; D055372:AMP-Activated Protein Kinases
keywords: NEDD9; epithelial-mesenchymal transition; lung cancer; metastasis