title: JAG1 Is Associated with Poor Survival through Inducing Metastasis in Lung Cancer.
abstract: JAG1 is a Notch ligand that plays a critical role in multiple signaling pathways. However, the functionality of JAG1 in non-small cell lung cancer (NSCLC) has not been investigated thoroughly. By comparison of gene transcripted RNA profiles in the cell line pair with differential invasion ability, we identified JAG1 as a potential metastasis enhancer in lung cancer. Ectopic expression of JAG1 on lung cancer cells enhanced cell migration and invasion as well as metastasis in vitro and in vivo. Conversely, knockdown of JAG1 with siRNA in highly invasive cancer cells led to the reduction of migration and invasion. In clinical analysis, JAG1 mRNA expression was higher in tumors than in adjacent normal tissues in 14 of 20 patients with squamous cell carcinoma (SCC). SCC patients with higher JAG1 transcription had poor overall survival than those with low-transcripted JAG1. Microarray analysis indicated that the enforced JAG1 transcription was associated with an elevated HSPA2 RNA transcription, which played a role in promoting cancer cell migration and invasion. In conclusion, this is the first study that demonstrated that JAG1 might act as a potential prognostic marker and JAG1/HSPA2 axis mediates lung cancer malignancy at least partly.
authors.affiliation: Institute of Molecular Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan.
authors.forename: Wen-Hsin
authors.initials: WH
authors.lastname: Chang
authors.affiliation: Department of Clinical Laboratory Sciences and Medical Biotechnology, College of Medicine, National Taiwan University, Taipei, Taiwan.
authors.forename: Bing-Ching
authors.initials: BC
authors.lastname: Ho
authors.affiliation: Department of Clinical Laboratory Sciences and Medical Biotechnology, College of Medicine, National Taiwan University, Taipei, Taiwan.
authors.forename: Yi-Jing
authors.initials: YJ
authors.lastname: Hsiao
authors.affiliation: Division of Thoracic Surgery, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.|Department of Surgery, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.
authors.forename: Jin-Shing
authors.initials: JS
authors.lastname: Chen
authors.affiliation: Department of Clinical Laboratory Sciences and Medical Biotechnology, College of Medicine, National Taiwan University, Taipei, Taiwan.
authors.forename: Chien-Hung
authors.initials: CH
authors.lastname: Yeh
authors.affiliation: Institute of Statistical Science, Academia Sinica, Taipei, Taiwan.
authors.forename: Hsuan-Yu
authors.initials: HY
authors.lastname: Chen
authors.affiliation: Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan.|Comprehensive Cancer Center, Taichung Veterans General Hospital, Taichung, Taiwan.
authors.forename: Gee-Chen
authors.initials: GC
authors.lastname: Chang
authors.affiliation: Department of Clinical Laboratory Sciences and Medical Biotechnology, College of Medicine, National Taiwan University, Taipei, Taiwan.|Department of Laboratory Medicine, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Kang-Yi
authors.initials: KY
authors.lastname: Su
authors.affiliation: Department of Clinical Laboratory Sciences and Medical Biotechnology, College of Medicine, National Taiwan University, Taipei, Taiwan.|Department of Laboratory Medicine, National Taiwan University Hospital, Taipei, Taiwan.|Department of Pathology, College of Medicine, National Taiwan University, Taipei, Taiwan.|Graduate Institute of Pathology, College of Medicine, National Taiwan University, Taipei, Taiwan.|Center for Optoelectronic Biomedicine, College of Medicine, National Taiwan University, Taipei, Taiwan.|Institute of Medical Device and Imaging, College of Medicine, National Taiwan University, Taipei, Taiwan.
authors.forename: Sung-Liang
authors.initials: SL
authors.lastname: Yu
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000235:genetics; D002135:Calcium-Binding Proteins / Q000235:genetics*; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics*; D000072100:Jagged-1 Protein; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology*; D008565:Membrane Proteins / Q000235:genetics*; D051379:Mice; D016513:Mice, SCID; D009361:Neoplasm Invasiveness / Q000235:genetics / Q000473:pathology; D009362:Neoplasm Metastasis / Q000235:genetics* / Q000473:pathology; D011379:Prognosis; D000072099:Serrate-Jagged Proteins
chemical_list: D014408:Biomarkers, Tumor; D002135:Calcium-Binding Proteins; D018840:HSP70 Heat-Shock Proteins; C091879:HSPA2 protein, human; D036341:Intercellular Signaling Peptides and Proteins; C000606273:JAG1 protein, human; C000606274:Jag1 protein, mouse; D000072100:Jagged-1 Protein; D008565:Membrane Proteins; D000072099:Serrate-Jagged Proteins