JAG1 is associated with poor survival through inducing metastasis in lung cancer
Journal
PLoS ONE
Journal Volume
11
Journal Issue
3
Pages
e0150355
Date Issued
2016
Author(s)
Chang W.-H.
Ho B.-C.
Hsiao Y.-J.
Yeh C.-H.
Chen H.-Y.
Chang G.-C.
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. ? 2016 Chang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Other Subjects
Jagged1; messenger RNA; RNA; small interfering RNA; calcium binding protein; heat shock protein 70; HSPA2 protein, human; JAG1 protein, human; Jag1 protein, mouse; membrane protein; protein Jagged 1; serrate jagged protein; signal peptide; tumor marker; animal experiment; animal model; animal tissue; Article; cancer cell; cancer cell culture; cancer tissue; cell invasion; cell migration; controlled study; genetic transfection; human; human cell; human tissue; immunoblotting; in vitro study; in vivo study; metastasis; microarray analysis; mouse; non small cell lung cancer; nonhuman; overall survival; plasmid; protein expression; reverse transcription polymerase chain reaction; squamous cell carcinoma; animal; cell motion; genetics; lung tumor; metastasis; non small cell lung cancer; pathology; prognosis; SCID mouse; tumor cell line; tumor invasion; Animals; Biomarkers, Tumor; Calcium-Binding Proteins; Carcinoma, Non-Small-Cell Lung; Carcinoma, Squamous Cell; Cell Line, Tumor; Cell Movement; HSP70 Heat-Shock Proteins; Humans; Intercellular Signaling Peptides and Proteins; Jagged-1 Protein; Lung Neoplasms; Membrane Proteins; Mice; Mice, SCID; Neoplasm Invasiveness; Neoplasm Metastasis; Prognosis; Serrate-Jagged Proteins
Type
journal article