Proteolytic Cleavage of Protein Tyrosine Phosphatase μ Regulates Glioblastoma Cell Migration
- 31 August 2009
- journal article
- Published by American Association for Cancer Research (AACR) in Cancer Research
- Vol. 69 (17), 6960-6968
- https://doi.org/10.1158/0008-5472.can-09-0863
Abstract
Glioblastoma multiforme (GBM), the most common malignant primary brain tumor, represents a significant disease burden. GBM tumor cells disperse extensively throughout the brain parenchyma, and the need for tumor-specific drug targets and pharmacologic agents to inhibit cell migration and dispersal is great. The receptor protein tyrosine phosphatase μ (PTPμ) is a homophilic cell adhesion molecule. The full-length form of PTPμ is down-regulated in human glioblastoma. In this article, overexpression of full-length PTPμ is shown to suppress migration and survival of glioblastoma cells. Additionally, proteolytic cleavage is shown to be the mechanism of PTPμ down-regulation in glioblastoma cells. Proteolysis of PTPμ generates a series of proteolytic fragments, including a soluble catalytic intracellular domain fragment that translocates to the nucleus. Only proteolyzed PTPμ fragments are detected in human glioblastomas. Short hairpin RNA–mediated down-regulation of PTPμ fragments decreases glioblastoma cell migration and survival. A peptide inhibitor of PTPμ function blocks fragment-induced glioblastoma cell migration, which may prove to be of therapeutic value in GBM treatment. These data suggest that loss of cell surface PTPμ by proteolysis generates catalytically active PTPμ fragments that contribute to migration and survival of glioblastoma cells. [Cancer Res 2009;69(17):6960–8]Keywords
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This publication has 48 references indexed in Scilit:
- p120 Catenin Recruits Cadherins to γ-Secretase and Inhibits Production of Aβ PeptidePublished by Elsevier BV ,2009
- Metalloproteinase- and γ-Secretase-mediated Cleavage of Protein-tyrosine Phosphatase Receptor Type ZPublished by Elsevier BV ,2008
- BCCIP associates with the receptor protein tyrosine phosphatase PTPµJournal of Cellular Biochemistry, 2008
- Tumor-Derived Extracellular Mutations of PTPRT/PTPρ Are Defective in Cell AdhesionMolecular Cancer Research, 2008
- A Role for the Cleaved Cytoplasmic Domain of E-cadherin in the NucleusPublished by Elsevier BV ,2008
- E-cadherin promotes retinal ganglion cell neurite outgrowth in a protein tyrosine phosphatase-mu-dependent mannerMolecular and Cellular Neuroscience, 2007
- Protein tyrosine phosphatase function: the substrate perspectiveBiochemical Journal, 2007
- Protein tyrosine phosphatases: from genes, to function, to diseaseNature Reviews Molecular Cell Biology, 2006
- Furin-, ADAM 10-, and γ-Secretase-Mediated Cleavage of a Receptor Tyrosine Phosphatase and Regulation of β-Catenin's Transcriptional ActivityMolecular and Cellular Biology, 2006
- Protein-tyrosine phosphatases and cancerNature Reviews Cancer, 2006