Nogo receptor–vimentin interaction: a novel mechanism for the invasive activity of glioblastoma multiforme

Nogo receptor (NgR) has been shown to inhibit the migration and invasion of human glioma cells. However, little is known regarding the regulatory mechanisms of NgR in glioblastoma multiforme (GBM). In this study, we propose a novel mechanism that regulates the maturation process of NgR through an interaction with vimentin. The inhibition of TGFβ1 activity by LY2109761 attenuated the migration/invasion of GBM cells by upregulating cell-surface NgR. Conversely, the treatment of GBM cells with TGFβ1 suppressed NgR maturation. We showed that NgR and vimentin interact, which could be a possible mechanism for the suppression of NgR maturation. The knockdown of vimentin suppressed the migration/invasion of GBM cells through the increased maturation of NgR. Finally, TCGA (The Cancer Genome Atlas) analysis also supported the association of NgR and vimentin. The maturation of NgR is regulated by the interaction of vimentin and NgR, which attenuates the invasive activity of GBM, and might be a potential therapeutic target for brain cancer. A mechanism that prevents the maturation of a protective cell surface protein during the spread of brain cancer could be a therapeutic target. Aggressive glioblastoma multiforme tumors spread quickly, lowering survival chances. The transforming growth factor-beta 1 (TGFβ1) protein is implicated in the rapid spread of cancer cells through the brain’s white matter fibers. However, cancer spread can be limited by the mature form of a protein receptor called nogo receptor (NgR), which is expressed on white matter cell surfaces. Using human glioblastoma cell cultures, Seung-Hoon Lee and Myung-Shin Lee at Eulji University School of Medicine, Daejeon, South Korea, and co-workers demonstrated how the interaction between NgR and another protein enhances TGFβ1 pathway activity and prevents NgR maturing. When the team inhibited TGFβ1, the interaction was disrupted, allowing NgR maturation and preventing tumor spread.