文献类型：期刊文献

英文题名：Protein tyrosine phosphatase receptor U (PTPRU) is required for glioma growth and motility

作者：Zhu, Zhichuan[1];Liu, Yongjie[1];Li, Kui[1];Liu, Jiwei[1];Wang, Hongtao[1];Sun, Bing[2];Xiong, Zhiqi[3];Jiang, Hualiang[1];Zheng, Jing[1];Hu, Zelan[1]

机构：[1]E China Univ Sci & Technol, Sch Pharm, Shanghai 200237, Peoples R China;[2]Fudan Univ, Huashan Hosp, Shanghai Neurosurg Ctr, Dept Neurosurg, Shanghai 200030, Peoples R China;[3]Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Neurosci, Shanghai 200031, Peoples R China

年份：2014

卷号：35

期号：8

起止页码：1901

外文期刊名：CARCINOGENESIS

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000343423000028)】；

基金：National Natural Science Foundation of China (31300904); China Postdoctoral Science Foundation grant (2014M551352) to Z.H.; the Exploratory Research Foundation of ECUST to J.Z.; the Shanghai Committee of Science and Technology (11DZ2260600).

语种：英文

摘要：The membrane protein tyrosine phosphatase receptor U (PTPRU) has been shown to function as a negative regulator of adhesion and proliferation in certain cancer cell types, primarily through its dephosphorylation of beta-catenin and inhibition of subsequent downstream signaling. In the present study, we set out to characterize the role of PTPRU in glioma and found that, while the expression of full-length PTPRU protein is low in these tumors, a number of non-full-length PTPRU isoforms are highly expressed. Among these isoforms, one in particular is localized to the nucleus, and its expression is increased in glioma tissues in a manner that positively correlates with malignancy grade. Short hairpin RNA knockdown of endogenous PTPRU in human and rat glioma cell lines suppressed proliferation, survival, invasion, migration, adhesion and vasculogenic tube formation in vitro, as well as intracranial tumor progression in vivo. In addition, knocking down PTPRU reduced tyrosine phosphorylation (pY) and transcriptional activity of beta-catenin, and we were able to specifically rescue the cell migration defect by expressing a LEF1-beta-catenin fusion protein in PTPRU-depleted cells. PTPRU knockdown also led to increased tyrosine pY of the E3 ubiquitin ligase c-Cbl and to the destabilization of several focal adhesion proteins. Taken together, our findings demonstrate that endogenous PTPRU promote glioma progression through their effect on beta-catenin and focal adhesion signaling.