SUMO-Specific Cysteine Protease 1 Promotes Epithelial Mesenchymal Transition of Prostate Cancer Cells via Regulating SMAD4 deSUMOylationReportar como inadecuado


SUMO-Specific Cysteine Protease 1 Promotes Epithelial Mesenchymal Transition of Prostate Cancer Cells via Regulating SMAD4 deSUMOylation


SUMO-Specific Cysteine Protease 1 Promotes Epithelial Mesenchymal Transition of Prostate Cancer Cells via Regulating SMAD4 deSUMOylation - Descarga este documento en PDF. Documentación en PDF para descargar gratis. Disponible también para leer online.

1

Department of Experimental Hematology, Beijing Institute of Radiation Medicine, Beijing 100850, China

2

Gene Therapy Program, Department of Medicine, NorthShore Research Institute, Evanston, IL 60201, USA





*

Authors to whom correspondence should be addressed.



Academic Editor: Carsten Stephan

Abstract In advanced prostate cancer, small ubiquitin-like modifier SUMO-specific cysteine protease 1 SENP1 is up-regulated. However, the role of SENP1 in regulating deSUMOylation of TGF-β-SMADs signaling is unknown. In this study, we developed a lentiviral vector, PLKO.1-shSENP1, to silence SENP1 in prostate cancer cells with high metastatic characteristics PC3M. Likewise, we also created an adenovirus vector, Ad5-F11p-SENP1 to over-express SENP1 in prostate cancer cells with low metastatic potential LNCaP. We showed that silencing of SENP1 promoted cellular apoptosis, and inhibited proliferation and migration of PC3M cells. Moreover, SENP1 silencing increased the SMAD4 expression at protein level, up-regulated E-cadherin and down-regulated Vimentin expression, indicating the inhibition of epithelial mesenchymal transition EMT. Furthermore, SMAD4 interference abolished SENP1-mediated up-regulation of E-cadherin, suggesting that SENP1 regulated E-cadherin expression via SMAD4. SENP1 over-expression in LNCaP cells reduced SMAD4 protein, and promoted EMT via decreasing E-cadherin and increasing Vimentin. Moreover, down-regulation of SMAD4 and E-cadherin were blocked, after transfection with two SUMOylation sites mutated SMAD4, suggesting that SENP1 might reduce SMAD4 levels to regulate E-cadherin expression via deSUMOylation of SMAD4. In conclusion, SENP1 deSUMOylated SMAD4 to promote EMT via up-regulating E-cadherin in prostate cancer cells. Therefore, SENP1 is a potential target for treatment of advanced prostate cancer. View Full-Text

Keywords: SENP1; deSUMOylation; EMT; SMAD4; E-cadherin; prostate cancer SENP1; deSUMOylation; EMT; SMAD4; E-cadherin; prostate cancer





Autor: Xiaoyan Zhang 1, Hao Wang 1, Hua Wang 1, Fengjun Xiao 1, Prem Seth 2, Weidong Xu 2, Qinghua Jia 1, Chutse Wu 1, Yuefeng Yang 1,* and Lisheng Wang 1,*

Fuente: http://mdpi.com/



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