59343

SENP2

SUMO-specific protease 2 (SENP2) is a deSUMOylation protease that plays an important role in the regulation of transforming growth factor-beta (TGF-beta) signaling. Aberrant TGF-beta signaling is common in human cancers and contributes to tumor metastasis by inducing an epithelial-mesenchymal transition (EMT). In previous studies, we demonstrated that SENP2 suppresses bladder cancer cell migration and invasion. However, little is known about whether SENP2 inhibits EMT by regulating TGF-beta signaling in bladder cancer progression. Here, we investigated the role of SENP2 in regulating TGF-beta signaling and bladder cancer metastasis in vitro and in vivo. We found that SENP2 is frequently downregulated in bladder cancer, especially in metastatic bladder cancer. SENP2 downregulation is associated with more aggressive phenotypes and poor patient outcomes. SENP2 knockdown results in a decrease of E-cadherin and an increase of N-cadherin and fibronectin at both transcript and protein levels, indicating that SENP2 negatively regulates EMT. On the contrary, SENP2 overexpression suppresses TGF-beta signaling and TGF-beta-induced EMT. We further demonstrated that SENP2 regulates TGF-beta signaling partly through deSUMOylation of TGFbeta receptor I (TGF-betaRI). Functionally, SENP2 suppresses bladder cancer cell invasion in vitro and tumor metastasis in vivo, acts as a tumor suppressor gene in bladder cancer. Our results establish a function of SENP2 in metastatic progression and suggest its candidacy as a new prognostic biomarker and target for clinical management of bladder cancer.CI - (c) 2017 Wiley Periodicals, Inc.