Fig. 3
From: Neddylation: a novel modulator of the tumor microenvironment
Neddylation acts as a modulator of cancer-associated fibroblasts (CAFs). a KEGG pathway enrichment analysis of down-regulated genes induced by MLN4924 in CAFs. CAFs were isolated from hepatocellular carcinoma (HCC) tissues, and treated with 1 μM MLN4924 for 12 h. b The expression of several inflammatory cytokines was reduced upon MLN4924 treatment. c-d Neddylation inhibition, either by MLN4924 treatment or siRNA-mediated depletion of NEDD8 or NAE1, suppressed CAFs migration. Conditioned medium (CM) collected from supernatants of HCC cells was used for chemotaxis assay. 5 × 104 isolated CAFs were placed into the upper chamber and treated with MLN4924 for 12 h at 37 °C. Cells that migrated were fixed and stained, followed by counting the cell number under a Leica microscope to measure. NC: Negative control. Scale bar for× 200 images, 50 μm