RRC ID 52640
著者 Torigoe H, Yamamoto H, Sakaguchi M, Youyi C, Namba K, Sato H, Shien K, Soh J, Suzawa K, Tomida S, Tsukuda K, Miyoshi S, Toyooka S.
タイトル Tumor-suppressive effect of LRIG1, a negative regulator of ErbB, in non-small cell lung cancer harboring mutant EGFR.
ジャーナル Carcinogenesis
Abstract Epidermal growth factor receptor (EGFR) is a member of the ErbB (HER) family that is known to play important roles in the pathogenesis of various human cancers. Mutations of the EGFR gene are commonly found as oncogenic driver mutations and have been targeted for treatment of non-small cell lung cancer (NSCLC). Leucine-rich repeat and immunoglobulin-like domain protein-1 (LRIG1) is a cell-surface protein that is known as a negative regulator of the ErbB (HER) family. In this study, we first confirmed that the expression levels of LRIG1 were much lower in NSCLC than in non-malignant cells or tissues. Next, we focused on the effect of LRIG1 in NSCLC. For this purpose, we established clones stably overexpressing LRIG1, using EGFR-mutant (HCC827, HCC4011 and NCI-H1975) and wild-type (A549) cells. Transfection of LRIG1 was associated with a decrease in the expression and phosphorylation levels of EGFR in the HCC827, HCC4011 and NCI-H1975 cells. It was also associated with strong suppression of the cell proliferative, invasive, migratory and tumorigenic potential of the HCC827 cells. On the other hand, no such effects were observed in the A549 cells. In addition, LRIG1 also downregulated the expression and phosphorylation levels of other tyrosine kinase receptors, such as HER2, HER3, MET and IGF-1R, and prevented the epithelial-to-mesenchymal transition induced by TGF-β in the HCC827 cells. These findings suggest that LRIG1 exerts important tumor-suppressive effects in EGFR-mutant NSCLC and has the potential to become a novel therapeutic target for EGFR-mutant NSCLC.
巻・号 39(5)
ページ 719-727
公開日 2018-5-3
DOI 10.1093/carcin/bgy044
PII 4931626
PMID 29546323
MeSH A549 Cells Carcinoma, Non-Small-Cell Lung / genetics* Cell Line, Tumor Cell Movement / genetics Cell Proliferation / genetics Down-Regulation / genetics Epithelial-Mesenchymal Transition / genetics ErbB Receptors / genetics Humans Lung Neoplasms / genetics* Membrane Glycoproteins / genetics* Mutation / genetics* Neoplasm Invasiveness / genetics Phosphorylation / genetics Receptor Protein-Tyrosine Kinases / genetics
IF 4.603
引用数 7
リソース情報
ヒト・動物細胞 PC-9(RCB4455)