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

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

Research output: Contribution to journalArticle

6 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)719-727
Number of pages9
JournalCarcinogenesis
Volume39
Issue number5
DOIs
Publication statusPublished - May 3 2018

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Epidermal Growth Factor Receptor
Non-Small Cell Lung Carcinoma
Leucine
Neoplasms
Proteins
Phosphorylation
erbB-1 Genes
Mutation
Epithelial-Mesenchymal Transition
Receptor Protein-Tyrosine Kinases
Immunoglobulin Domains
Transfection
Membrane Proteins
Down-Regulation
Clone Cells

ASJC Scopus subject areas

  • Cancer Research

Cite this

Tumor-suppressive effect of LRIG1, a negative regulator of ErbB, in non-small cell lung cancer harboring mutant EGFR. / Torigoe, Hidejiro; Yamamoto, Hiromasa; Sakaguchi, Masakiyo; Youyi, Chen; Namba, Kei; Sato, Hiroki; Shien, Kazuhiko; Sou, Junichi; Suzawa, Ken; Tomida, Shuta; Tsukuda, Kazunori; Miyoshi, Shinichiro; Toyooka, Shinichi.

In: Carcinogenesis, Vol. 39, No. 5, 03.05.2018, p. 719-727.

Research output: Contribution to journalArticle

Torigoe, Hidejiro ; Yamamoto, Hiromasa ; Sakaguchi, Masakiyo ; Youyi, Chen ; Namba, Kei ; Sato, Hiroki ; Shien, Kazuhiko ; Sou, Junichi ; Suzawa, Ken ; Tomida, Shuta ; Tsukuda, Kazunori ; Miyoshi, Shinichiro ; Toyooka, Shinichi. / Tumor-suppressive effect of LRIG1, a negative regulator of ErbB, in non-small cell lung cancer harboring mutant EGFR. In: Carcinogenesis. 2018 ; Vol. 39, No. 5. pp. 719-727.
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AU - Youyi, Chen

AU - Namba, Kei

AU - Sato, Hiroki

AU - Shien, Kazuhiko

AU - Sou, Junichi

AU - Suzawa, Ken

AU - Tomida, Shuta

AU - Tsukuda, Kazunori

AU - Miyoshi, Shinichiro

AU - Toyooka, Shinichi

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