Protein tyrosine phosphatase receptor U (PTPRU) is required for glioma growth and motility.

Abstract

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 β-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 β-catenin, and we were able to specifically rescue the cell migration defect by expressing a LEF1-β-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 β-catenin and focal adhesion signaling.

• Authors: Zhichuan Zhu, Yongjie Liu, Kui Li, Jiwei Liu, Hongtao Wang, Bing Sun, Zhiqi Xiong, Hualiang Jiang, Jing Zheng, Zelan Hu
• Journal: Carcinogenesis (Carcinogenesis) Vol. 35 Issue 8 Pg. 1901-10 (Aug 2014) ISSN: 1460-2180 [Electronic] England
• PMID: 24876153 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: [email protected].

Chemical References

• RNA, Messenger
• RNA, Small Interfering
• PTPRU protein, human
• Receptor-Like Protein Tyrosine Phosphatases, Class 2

Topics

• Animals
• Apoptosis
• Blotting, Western
• Brain (metabolism)
• Brain Neoplasms (genetics, metabolism, pathology)
• Cell Cycle
• Cell Movement
• Cell Proliferation
• Fluorescent Antibody Technique
• Glioma (genetics, metabolism, pathology)
• Humans
• Immunoprecipitation
• Male
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• RNA, Messenger (genetics)
• RNA, Small Interfering (genetics)
• Real-Time Polymerase Chain Reaction
• Receptor-Like Protein Tyrosine Phosphatases, Class 2 (antagonists & inhibitors, genetics, metabolism)
• Reverse Transcriptase Polymerase Chain Reaction
• Tumor Cells, Cultured
• Xenograft Model Antitumor Assays