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양미정 남기택(의생명과학부) Am J Pathol
등록일 : 2018-09-27 오전 11:27:00       조회 : 376
첨   부 :
제1저자 유성숙(의생명과학부), 양미정(의생명과학부, 의과학과 졸, BK21), 임경민(이화여대)
교신저자 남기택(의생명과학부)

Am J Pathol. 2018 Sep 21. pii: S0002-9440(18)30279-7. doi: 10.1016/j.ajpath.2018.08.006.
Expression of Lrig1, a negative regulator of EGFR, is dynamically altered during different stages of gastric carcinogenesis.
Yu S1, Yang M1, Lim KM2, Cho Y1, Kim H1, Lee K3, Jeong SH4, Coffey RJ5, Goldenring JR6, Nam KT7.

Author information
1Severance Biomedical Science Institute, Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul 03722, Korea.2College of Pharmacy, Ewha Womans University, Seoul 03760, Korea.3Department of Biomedical Science, Hallym University, Chuncheon 24252, Korea.4Department of Surgery, Gyeongsang National University Changwon Hospital, Gyeongsang National University, Changwon 51472, Korea.5Epithelial Biology Center and Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN, 37232, USA.6Epithelial Biology Center and Section of Surgical Science, Vanderbilt University School of Medicine, Nashville, TN, 37232, USA.7Severance Biomedical Science Institute, Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul 03722, Korea. Electronic address: kitaek@yuhs.ac.

Abstract
Leucine-rich repeats and immunoglobulin-like domains 1 (Lrig1) is a transmembrane protein that antagonizes epidermal growth factor receptor (EGFR) 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 mouse spasmolytic polypeptide-expressing metaplasia (SPEM) model and 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 SPEM lesions but disappearing in intestinal metaplasia and cancer lesions, and the increase was concomitant with the up-regulation of EGFR. 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 with gastric carcinogenesis and may play a vital role as a tumor suppressor through modulating EGFR activity.
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