Abstract 5984: MT1-MMP cooperates with TGF-beta receptor-mediated signaling to trigger SNAIL and induce epithelial-to-mesenchymal-like transition in U87 glioblastoma cells

Abstract

Abstract Transforming growth factor (TGF)-β triggers metastasis through epithelial-to-mesenchymal transition (EMT) to which a role for a membrane type-1 matrix metalloproteinase (MT1-MMP) has been associated. While EMT cooperates with MMP activity in glioblastoma multiforme, the molecular crosstalk between TGF-β signaling and MT1-MMP however remains poorly understood. Here, the existence of common EMT biomarkers, induced through TGF-β and MT1-MMP inducer Concanavalin A (ConA), was explored using RNA-seq analysis and differential gene arrays in human U87 glioblastoma cells. TGF-β and ConA triggered SNAIL and Fibronectin expressions in a dose-dependent manner. Those inductions were antagonized by the TGF-β receptor kinase inhibitor Galunisertib, the JAK/STAT inhibitors AG490 and Tofacitinib, and by the diet-derived epigallocatechin gallate (EGCG). Transient gene silencing of MT1-MMP prevented the induction of SNAIL by ConA and abrogated TGF-β-induced cell chemotaxis. Moreover, ConA induced STAT3 and Src phosphorylation suggesting these pathways to be involved in the MT1-MMP-mediated signaling axis that led to SNAIL induction. Our findings highlight a new signaling axis linking MT1-MMP to TGF-β-mediated EMT-like induction in glioblastoma cells, which process can be prevented by the diet-derived EGCG Citation Format: Souad Djediai, Narjara Gonzalez Suarez, Zoé Joly-Lopez, Borhane Annabi. MT1-MMP cooperates with TGF-beta receptor-mediated signaling to trigger SNAIL and induce epithelial-to-mesenchymal-like transition in U87 glioblastoma cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5984.