Lumican promotes gastric cancer progression by regulating the ERK pathway

Abstract

Globally, gastric cancer (GC) remains a major cause of death. Our prior study found lumican to be an important independent predictor of GCs poor overall survival and bioinformatics analysis suggested the MAPK pathway as a signaling cascade linked to lumican function. In our study, we observed that lumican exhibited a significant elevation in GC tissues and cells, hastening tumor proliferation in vivo in comparison to control groups. We also observed that knockdown of lumican effectively inhibited the proliferation, migration and invasion of AGS cells. On the contrary, overexpression of lumican promoted the proliferation, migration and invasion of AGS cells. We clarified that lumican was upstream of ERK in the MAPK pathway. In rescue assays, TBHQ further enhanced the promoting effect of lumican overexpression on cell migration and invasion and the increased expression of ERK 1/2 or p-ERK 1/2 levels. However, the increased expression of ERK 1/2 or p-ERK 1/2, migration and invasion were completely blocked by GDC-0994 in lumicanoverexpressing AGS cells with TBHQ treated. Molecular docking prediction revealed that the amino acid sequence of lumican binding to ERK1/2 may also regulate the ERK pathway. In conclusions, lumican is highly expressed in GC and promotes the proliferation, migration and invasion of GC cells by regulating ERK pathway. Consequently, lumican emerges as pivotal indicators for both diagnosis and treatment in GC cases.