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Cancer-associated fibroblasts (CAFs) are major components of the tumor stroma and regulators of tumor progression. However, the molecular mechanism by which CAFs promote gastric cancer progression should be further explored. In our study, we found that interleukin-11 (IL-11) secretion was significantly increased when CAFs were co-cultured with gastric cancer cells. Co-culture system-derived IL-11 promoted the migration and invasion of gastric cancer cells, whereas the increase of migration and invasion was attenuated by a neutralizing antibody of IL-11 or inhibition of JAK/STAT3 and MAPK/ERK pathways with specific inhibitors. Taken together, these results revealed that CAFs play a significant role in the gastric cancer progression in the tumor microenvironment through IL-11-STAT3/ERK signaling by upregulating MUC1. Also, IL-11 targeted therapy can achieve an effective treatment against gastric cancer indirectly by exerting their action on stromal fibroblasts.The interaction of CAFs and GC cells promotes the secretion of IL-11.IL-11 was significantly increased in both CAFs and GC cells of the co-culture system.CAFs enhance the migration and invasion of GC cells via the expression of IL-11.CAFs promote migration and invasion of GC cells via up-regulation of MUC1.