Proteolytic cleavage of protein tyrosine phosphatase μ regulates glioblastoma cell migration

Adam M. Burgoyne, Polly J. Phillips-Mason, Susan M. Burden-Gulley, Shenandoah Robinson, Andrew E. Sloan, Robert H. Miller, Susann M. Brady-Kalnay

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)6960-6968
Number of pages9
JournalCancer Research
Volume69
Issue number17
DOIs
StatePublished - Sep 1 2009

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ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Burgoyne, A. M., Phillips-Mason, P. J., Burden-Gulley, S. M., Robinson, S., Sloan, A. E., Miller, R. H., & Brady-Kalnay, S. M. (2009). Proteolytic cleavage of protein tyrosine phosphatase μ regulates glioblastoma cell migration. Cancer Research, 69(17), 6960-6968. https://doi.org/10.1158/0008-5472.CAN-09-0863