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Esophageal cancer is one of the most frequent malignant tumors of the digestive tract.The metastasis is the leading factor to the high mortality in esophageal cancer.However,the involved mechanism is still elusive to us although great advancement has been achieved in the clinical treatment.In the current study,we found that the Gremlin1 (GREM1) were overexpression in human esophageal squamous carcinoma cells.Conditional medium from mesenchymal stem cells (MSCs) could enhance the malignancy of esophageal tumor in vivo as well as the migration and invasion of esophageal cancer cells ECa109 and TE-1 in vitro.Furthermore,GREM1 silencing had an antitumor effect on MSCs-induced malignancy in ECal09 and TE-1 xenografts.In vitro experiments proved that downregulation of Gremlin1 (GREM1) in MSCs reversed the aggravating malignancy,the proliferation,invasion and migration of ECa109.This process was accompanied by the epithelial-mesenchymal transition (EMT) in the ECa109 cells with the alteration in expression level of mesenchymal and epithelial markers.TGF-β and BMP signaling participated in the GREM1 downregulation-induced antitumor effect.This study provided the experimental evidence to show the potential clinical application of GREM1 silencing within MSCs in the treatment of esophageal cancer.