論文

査読有り 国際誌
2018年5月3日

Tumor-suppressive effect of LRIG1, a negative regulator of ErbB, in non-small cell lung cancer harboring mutant EGFR.

Carcinogenesis
  • Hidejiro Torigoe
  • ,
  • Hiromasa Yamamoto
  • ,
  • Masakiyo Sakaguchi
  • ,
  • Chen Youyi
  • ,
  • Kei Namba
  • ,
  • Hiroki Sato
  • ,
  • Kazuhiko Shien
  • ,
  • Junichi Soh
  • ,
  • Ken Suzawa
  • ,
  • Shuta Tomida
  • ,
  • Kazunori Tsukuda
  • ,
  • Shinichiro Miyoshi
  • ,
  • Shinichi Toyooka

39
5
開始ページ
719
終了ページ
727
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1093/carcin/bgy044

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.

リンク情報
DOI
https://doi.org/10.1093/carcin/bgy044
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/29546323
ID情報
  • DOI : 10.1093/carcin/bgy044
  • ISSN : 0143-3334
  • PubMed ID : 29546323

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