Extracellular AGR2 triggers lung tumour cell proliferation through repression of p21CIP1

The human Anterior GRadient 2 (AGR2) protein is an Endoplasmic Reticulum (ER)-resident which belongs to the Protein-Disulfide Isomerase (PDI) superfamily and involved productive folding in ER. As such AGR2, often found overexpressed adenocarcinomas, contributes tumour development by enhancing ER proteostasis. We previously demonstrated that AGR2 secreted (extracellular (eAGR2)) microenvironment plays extracellular roles independent of its functions. Herein, we show eAGR2 triggers cell proliferation characterize underlying molecular mechanisms. demonstrate enhances growth repressing suppressor p21CIP1. Our findings shed light on a novel mechanism through behaves as factor microenvironment, independently function, thus promoting repression results provide rationale for targeting eAGR2/p21CIP1-based signalling potential therapeutic target impede growth.