Expression of LRIG1, a Negative Regulator of EGFR, Is Dynamically Altered during Different Stages of Gastric Carcinogenesis

Sungsook Yu, Mijeong Yang, Kyung Min Lim, Yejin Cho, Hyunji Kim, Keunwook Lee, Sang Ho Jeong, Robert J. Coffey, James R. Goldenring, KiTaek Nam

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Leucine-rich repeats and immunoglobulin-like domains (LRIG)-1 is a transmembrane protein that antagonizes epidermal growth factor receptor signaling in epithelial tissues. LRIG1 is down-regulated in various epithelial cancers, including bladder, breast, and colorectal cancer, suggesting that it functions as a tumor suppressor. However, its role in gastric carcinogenesis is not well understood. Here, we investigated the changes in LRIG1 expression during the stages of gastric cancer. We used a DMP-777–induced spasmolytic polypeptide-expressing metaplasia mouse model and a tissue array of human gastric cancer lesions. The effects of LRIG1 knockdown were also assessed using the human gastric cancer cell line SNU638 in a xenograft model. LRIG1 expression varied over the course of gastric carcinogenesis, increasing in spasmolytic polypeptide-expressing metaplasia lesions but disappearing in intestinal metaplasia and cancer lesions, and the increase was concurrent with the up-regulation of epidermal growth factor receptor. In addition, LRIG1 knockdown promoted the tumorigenic potential in vitro, which was manifested as increased proliferation, invasiveness, and migration as well as increased tumor size in vivo in the xenograft model. Furthermore, LRIG1 expression was determined to be a positive prognostic biomarker for the survival of gastric cancer patients. Collectively, our findings indicate that LRIG1 expression is closely related wto gastric carcinogenesis and may play a vital role as a tumor suppressor through the modulation of epidermal growth factor receptor activity.

Original languageEnglish
Pages (from-to)2912-2923
Number of pages12
JournalAmerican Journal of Pathology
Volume188
Issue number12
DOIs
Publication statusPublished - 2018 Dec 1

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Stomach Neoplasms
Stomach
Metaplasia
Carcinogenesis
Epidermal Growth Factor Receptor
Heterografts
Urinary Bladder Neoplasms
Intestinal Neoplasms
Neoplasms
Leucine
Colorectal Neoplasms
Up-Regulation
Epithelium
Biomarkers
Breast Neoplasms
Cell Line
Survival
Proteins
spasmolytic polypeptide

All Science Journal Classification (ASJC) codes

  • Pathology and Forensic Medicine

Cite this

Yu, Sungsook ; Yang, Mijeong ; Lim, Kyung Min ; Cho, Yejin ; Kim, Hyunji ; Lee, Keunwook ; Jeong, Sang Ho ; Coffey, Robert J. ; Goldenring, James R. ; Nam, KiTaek. / Expression of LRIG1, a Negative Regulator of EGFR, Is Dynamically Altered during Different Stages of Gastric Carcinogenesis. In: American Journal of Pathology. 2018 ; Vol. 188, No. 12. pp. 2912-2923.
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Expression of LRIG1, a Negative Regulator of EGFR, Is Dynamically Altered during Different Stages of Gastric Carcinogenesis. / Yu, Sungsook; Yang, Mijeong; Lim, Kyung Min; Cho, Yejin; Kim, Hyunji; Lee, Keunwook; Jeong, Sang Ho; Coffey, Robert J.; Goldenring, James R.; Nam, KiTaek.

In: American Journal of Pathology, Vol. 188, No. 12, 01.12.2018, p. 2912-2923.

Research output: Contribution to journalArticle

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