Glioblastoma invasion factor ODZ1 is induced by microenvironmental signals through activation of a Stat3-dependent transcriptional pathway

Abstract We have previously shown that the transmembrane protein ODZ1 serves for glioblastoma (GBM) cells to invade surrounding tissue through activation of RhoA/ROCK pathway. However, transcriptional machinery used by GBM regulate expression is unknown. Here we show interaction with tumor microenvironment elements, mainly activated monocytes IL-6 secretion, and extracellular matrix fibronectin, induces Stat3 pathway upregulates which results in cell migration. This signaling route abrogated blocking receptor, inhibiting Jak kinases or knocking down Stat3. Furthermore, identified a responsive element gene promoter, about 1 kb from transcription start site. Luciferase-reporter assays confirmed promoter responds presence monocytic this greatly reduced when site mutated following treatment neutralizing anti-IL-6 receptor antibody transfecting dominant negative variant Overall, monocyte-secreted fibronectin activate axis Stat3-ODZ1 promote migration cells. first described mechanism invasion factor ODZ1.