The chaperone GRP94 interacts with the proprotein convertase furin and regulates TGF-beta maturation in human primary M2 macrophages.

ABSTRACT: Transforming growth factor-beta (TGFβ) is a major immunosuppressive cytokine produced by various cell types, including regulatory T cells (Tregs) and M2 macrophages. In Tregs, GRP94 is known as a key protein regulating TGFβ expression by chaperoning both the TGFβ docking receptor, GARP, and the integrin αvβ8. We previously reported that GRP94 inhibition in a triple-negative breast cancer (TNBC) murine model induced a decrease in intra-tumoral CD206 + M2-like macrophages that correlated with a decrease in collagen content, an increase in CD8+ cells in tumors and a reduced tumor volume. Here, we investigated the impact of GRP94 inhibition on TGFβ expression focusing on a possible interaction with furin, a proprotein convertase responsible for the first step in TGFβ maturation. We demonstrate

SUBMITTER: Baverel V 

PROVIDER: S-EPMC12706012 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature