The mechanisms underlying the crosstalk of oral squamous cell carcinoma (OSCC) cells and fibroblasts remain poorly investigated. We identified that ectopic expression of interferon stimulated gene 15 (ISG15) enhanced expression of collagen and alpha-smooth muscle actin (alpha-SMA) in ISG15-expressing tumors. The in vivo experiments confirmed fibroblast recruitment in ISG15-expressing OSCC tissues. And, exogenous ISG15 induced fibroblast migration, morphological changes and vimentin expression. Using geneset enrichment analysis (GSEA), the glycolysis pathway was enriched in ISG15-treated fibroblasts. The glucose consumption and lactate production were amplified in ISG15-treated fibroblast. Also, lactate release and fibroblast migration were blocked by 2-deoxy-d-glucose (2-DG), a competitive inhibitor of glucose metabolism. Furthermore, CD11a, a subunit of ISG15 receptor, lymphocyte function-associated antigen-1 (LFA-1), was involved in ISG15-meidated glycolysis and fibroblast migration. Our findings uncovered that OSCC-derived ISG15 bond to its receptors, LFA-1 on fibroblasts to activate glycolysis reprogramming and finally promote fibroblast movement.
