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

Title
Expression of LRIG1, a Negative Regulator of EGFR, Is Dynamically Altered during Different Stages of Gastric Carcinogenesis
Authors
Yu, SungsookYang, MijeongLim, Kyung-MinCho, YejinKim, HyunjiLee, KeunwookJeong, Sang-HoCoffey, Robert J.Goldenring, James R.Nam, Ki Taek
Ewha Authors
임경민
SCOPUS Author ID
임경민scopus
Issue Date
2018
Journal Title
AMERICAN JOURNAL OF PATHOLOGY
ISSN
0002-9440JCR Link

1525-2191JCR Link
Citation
AMERICAN JOURNAL OF PATHOLOGY vol. 188, no. 12, pp. 2912 - 2923
Publisher
ELSEVIER SCIENCE INC
Indexed
SCI; SCIE; SCOPUS WOS
Document Type
Article
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 metaptasia 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 metaptasia 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.
DOI
10.1016/j.ajpath.2018.08.006
Appears in Collections:
약학대학 > 약학과 > Journal papers
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