The Protein Tyrosine Phosphatase TCPTP Suppresses the Tumorigenicity of Glioblastoma Cells Expressing a Mutant Epidermal Growth Factor Receptor*

Glioblastoma multiforme (GBM) is the most aggressive type of glioma and GBMs frequently contain amplifications or mutations of the EGFR gene. The most common mutation results in a truncated receptor tyrosine kinase known as ΔEGFR that signals constitutively and promotes GBM growth. Here, we report that the 45-kDa variant of the protein tyrosine phosphatase TCPTP (TC45) can recognize ΔEGFR as a cellular substrate. TC45 dephosphorylated ΔEGFR in U87MG glioblastoma cells and inhibited mitogen-activated protein kinase ERK2 and phosphatidylinositol 3-kinase signaling. In contrast, the substrate-trapping TC45-D182A mutant, which is capable of forming stable complexes with TC45 substrates, suppressed the activation of ERK2 but not phosphatidylinositol 3-kinase. TC45 inhibited the proliferation and anchorage-independent growth of ΔEGFR cells but TC45-D182A only inhibited cellular proliferation. Notably, neither TC45 nor TC45-D182A inhibited the proliferation of U87MG cells that did not express ΔEGFR. ΔEGFR activity was necessary for the activation of ERK2, and pharmacological inhibition of ERK2 inhibited the proliferation of ΔEGFR-expressing U87MG cells. Expression of either TC45 or TC45-D182A also suppressed the growth of ΔEGFR-expressing U87MG cells in vivo and prolonged the survival of mice implanted intracerebrally with these tumor cells. These results indicate that TC45 can inhibit the ΔEGFR-mediated activation of ERK2 and suppress the tumorigenicity of ΔEGFR-expressing glioblastoma cells in vivo.

• Publication year

  2001

• Venue

  Journal of Biological Chemistry

• Publication date

  2001-12-07

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1074/JBC.M106571200PMID 11514572
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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