Moreover, Jab1/CSN5 can induce the degradation of two important downstream molecules, Smad4 and Smad7, and affect transforming growth factor-b (TGFb) signaling which is also influenced by various factors in the tumor microenvironment, and might contribute to lymphatic and distant metastasis [7, 37]. This evidence concerns the gene TGFB1 and neoplasm.