Expression of EGFR negative regulator, Lrig1 in gastric carcinogenesis

Abstract

Leucine-rich repeats and immunoglobulin-like domains 1 (LRIG1) is a transmembrane protein that antagonises EGFR signaling by downregulating receptor levels. Recent studies have proposed that Lrig1 marks predominately non-cycling, long-lived stem cells located at the crypt +4 quiescent intestinal stem cells by lineage tracing.Multiple groups have reported that Lrig1 expression is downregulated in several cancers, including bladder, lung, renal, breast, and colorectal cancer. These results suggested that Lrig1, known as a tumor suppressor, playsanimportant role in maintaining intestinal epithelial homeostasis.However, the function of Lrig1 in gastric mucosa is not well understood yet. Here, I investigated the alternative Lrig1 expression using DMP-777 treated mouse SPEM model in gastric carcinogenesis by in situ hybridization.I also observed thatthe altered expression of Lrig1 during human gastric cancer developmentbyin situhybridization and immunohistochemistry. The results showed the Lrig1 expression was increased in SPEM lesion while it was lost in IM and gastric cancer lesion, during gastric carcinogenesis.However, on the contrary to Lrig1, EGFR was upregulated throughout gastric carcinogenesis. Furthermore, I examined the effects of Lrig1 knockdown on proliferation of gastric cancer cell lines. The knockdown of Lrig1 promoted cell growth rate in gastric cancer cell lines. From our findings indicate Lrig1 as a negative regulator of EGFR,mayact a critical point in metaplastic progression