Expression of Lrig1, a negative regulator of EGFR, is dynamically altered during different stages of gastric carcinogenesis.

Expression of Lrig1, a negative regulator of EGFR, is dynamically altered during different stages of gastric carcinogenesis. Am J Pathol. 2018 Sep 21;: Authors: Yu S, Yang M, Lim KM, Cho Y, Kim H, Lee K, Jeong SH, Coffey RJ, Goldenring JR, Nam KT 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. Furthermo...
Source: The American Journal of Pathology - Category: Pathology Authors: Tags: Am J Pathol Source Type: research