The transforming growth factor (TGF)-β signaling events are well known to control diverse processes and numerous responses,such as cell proliferation,differentiation,apoptosis,and migration.TGF-β signaling plays context-dependent roles in cancer:in pre-malignant cells TGF-β primarily functions as a tumor suppressor,while in the later stages of cancer TGF-β signaling promotes invasion and metastasis.Recent studies have also suggested that the cross-talk between TGF-β signaling and other signaling pathways,such as Hippo,Wnt,EGFR/RAS,and PI3K/AKT pathways,may substantially contribute to our current understanding of TGF-β signaling and cancer.As a result of the wide-ranging effects of TGF-β,blockade of TGF-β and its downstream signaling components provides multiple therapeutic opportunities.Therefore,the outlook for anti-TGF-β signaling therapy for numerous diseases appears bright and will provide valuable information and thinking on the drug molecular design.In this review,we focus on recent insights into the regulation of TGF-β signaling in cancer metastasis which may contribute to the development of novel cancer-targeting therapies.