USP33, a new player in lung cancer, mediates Slit-Robo signaling  

作　　者：Pushuai Wen Ruirui Kong Jianghong Liu Li Zhu Xiaoping Chen Xiaofei Li Yongzhan Nie Kaichun WU Jane Y. Wu 

机构地区：[1]State Key Laboratory of Brain and Cognitive Science, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China [2]Department of Neurology, Center for Genetic Medicine, Lurie Cancer Center, Northwestern University Feinberg School of Medicine, 303 E. Chicago Ave., Chicago, IL 60611, USA [3]Department of Thoracic Surgery, Tangdu Hospital, Fourth Military Medical University, Xi'an 710038, China [4]State Key Laboratory of Cancer Biology and Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an 710032, China [5]University of Chinese Academy of Sciences, Beijing 100049, China [6]Department of Pathophysiology, Liaoning Medical University, Jinzhou 121001, China

出　　处：《Protein & Cell》2014年第9期704-713,共10页蛋白质与细胞（英文版）

基　　金：ACKNOWLEDGEMENTS We gratefully thank Dr. Zhipei Zhang for the assistance in lung cancers sample collection. We thank Mang Zheng for technical assistance. We thank other members of Wu lab for stimulating dis- cussion and helpful suggestions. This work was supported by the National Basic Research Program （973 Program） （2010CB529603 and 2013CB917803） and the National Natural Science Foundation of China （Grant No. 91132710）. RK was supported by China Post- doctoral Science Foundation （20110490615）. JYW is supported by NIH （Nos. RO1AG033004 and RO1CA175360）. JYW designed the study; PW, XC and RK performed the experiments and analyzed the data; XL, YN and KW provided tissue samples and important suggestions; LZ, JL and JYW supervised the experiments and analyzed the data; PW and JYW wrote the paper.

摘　　要：Ubiquitin specific protease 33 （USP33） is a multifunctional protein regulating diverse cellular processes. The expression and role of USP33 in lung cancer remain unexplored. In this study, we show that USP33 is down-regulated in multi- ple cohorts of lung cancer patients and that low expression of USP33 is associated with poor prognosis. USP33 medi- ates Slit-Robo signaling in lung cancer cell migration. Downregulation of USP33 reduces the protein stability of Robol in lung cancer cells, providing a previously unknown mechanism for USP33 function in mediating Slit activity in lung cancer ceils. Taken together, USP33 is a new player in lung cancer that regulates Slit-Robo signaling. Our data suggest that USP33 may be a candidate tumor suppressor for lung cancer with potential as a prognostic marker.Ubiquitin specific protease 33 （USP33） is a multifunctional protein regulating diverse cellular processes. The expression and role of USP33 in lung cancer remain unexplored. In this study, we show that USP33 is down-regulated in multi- ple cohorts of lung cancer patients and that low expression of USP33 is associated with poor prognosis. USP33 medi- ates Slit-Robo signaling in lung cancer cell migration. Downregulation of USP33 reduces the protein stability of Robol in lung cancer cells, providing a previously unknown mechanism for USP33 function in mediating Slit activity in lung cancer ceils. Taken together, USP33 is a new player in lung cancer that regulates Slit-Robo signaling. Our data suggest that USP33 may be a candidate tumor suppressor for lung cancer with potential as a prognostic marker.

关 键 词：USP33 SLIT ROBO lung cancer Slit-Robosignaling tumor suppressor prognostic marker 

分 类 号：Q782[生物学—分子生物学] TP242[自动化与计算机技术—检测技术与自动化装置]