Smad7 suppresses melanoma lung metastasis by impairing Tregs migration to the tumor microenvironment

Transforming growth factor β (TGF-β) signaling plays critical roles in both physiological and pathological conditions. In the tumor microenvironment, TGF-β are well demonstrated as a tumor inducer, which also promote tumor growth and metastasis. SMAD family is an important TGF-β signalling transducer, which consists of receptor-regulated SMADs (R-SMADs), common-mediator SMADs (co-SMADs), and inhibitory SMADs (I-SMADs). Smad7 is one of the I-SMADs which has been proved to block TGF-β signalling transduction in both tumor cells and immune cells. Accumulated evidence has suggested SMAD7 acted as a tumor suppressor in various cancer types, such as colorectal cancer, pancreatic cancer and skin melanoma, etc. However, the role of SMAD7 in melanoma lung metastasis has not been well studied. Here, we first investigated the role of SMAD7 on tumor cell viability by overexpressing SMAD7 in murine melanoma cell line B16-F10. Our results showed that SMAD7 overexpression slightly impaired B16-F10 cells growth, promoted cell apoptosis and arrested the cell cycle at S phase. In vivo study showed that SMAD7 overexpression inhibited B16-F10 lung metastasis. Further mechanism study suggested that SMAD7 promoted T cells activation by decreasing regulatory T cells (Tregs) infiltrating into the tumor microenvironment. In summary, our results proved that tumor cell derived SMAD7 inhibited melanoma lung metastasis by impairing the migration capacity of Tregs.