title: ADAM10 overexpression in human non-small cell lung cancer correlates             with cell migration and invasion through the activation of the Notch1 signaling             pathway.
abstract: A disintegrin and metalloproteinase 10 (ADAM10) was identified as a key protease in the ectodomain shedding of various substrates, such as Notch1 protein, ErbB2 and E-cadherin, which are important in the development of non-small cell lung cancer (NSCLC). The aim of this study was to investi-gate the role of ADAM10 in NSCLC metastasis.We characterized the expression of ADAM10 and Notch1 in human NSCLC tissues in vivo. Immunohistochemical analysis indicated that ADAM10 expression was significantly increased in the NSCLC tissues, particularly in the metastatic tissues. Futhermore, ADAM10 overexpression positively correlated with Notch1 expression in the NSCLC tissues. The in vitro downregulation of ADAM10 expression using ADAM10 short hairpin RNA (shRNA) reduced the migration and invasion of NSCLC cells. We present further evidence that ADAM10 promotes NSCLC cell migration and invasion via the activation of the Notch1 signaling pathway. Taken together, our results suggest that ADAM10 may serve as a potential target for the therapeutic intervention of NSCLC metastasis. The data provided in this study may aid in the further understanding of the function of ADAM10 in the progression of NSCLC and open new perspectives for the diagnosis and treatment of NSCLC.
authors.affiliation: Department of Biochemistry and Molecular Biology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, PR China.
authors.forename: Jianli
authors.initials: J
authors.lastname: Guo
authors.forename: Lei
authors.initials: L
authors.lastname: He
authors.forename: Ping
authors.initials: P
authors.lastname: Yuan
authors.forename: Peng
authors.initials: P
authors.lastname: Wang
authors.forename: Yanjun
authors.initials: Y
authors.lastname: Lu
authors.forename: Fangli
authors.initials: F
authors.lastname: Tong
authors.forename: Yu
authors.initials: Y
authors.lastname: Wang
authors.forename: Yanhua
authors.initials: Y
authors.lastname: Yin
authors.forename: Jun
authors.initials: J
authors.lastname: Tian
authors.forename: Jun
authors.initials: J
authors.lastname: Sun
mesh_terms: D051722:ADAM Proteins / Q000235:genetics / Q000378:metabolism*; D000072197:ADAM10 Protein; D053829:Amyloid Precursor Protein Secretases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002465:Cell Movement; D004151:Dipeptides / Q000494:pharmacology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D034622:RNA Interference; D034741:RNA, Small Interfering; D051881:Receptor, Notch1 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D004151:Dipeptides; D008565:Membrane Proteins; C419410:N-(N-(3,5-difluorophenacetyl)alanyl)phenylglycine tert-butyl ester; C497761:NOTCH1 protein, human; D034741:RNA, Small Interfering; D051881:Receptor, Notch1; D053829:Amyloid Precursor Protein Secretases; D051722:ADAM Proteins; D000072197:ADAM10 Protein; C491236:ADAM10 protein, human