TY - JOUR
T1 - Proteolytic cleavage of protein tyrosine phosphatase μ regulates glioblastoma cell migration
AU - Burgoyne, Adam M.
AU - Phillips-Mason, Polly J.
AU - Burden-Gulley, Susan M.
AU - Robinson, Shenandoah
AU - Sloan, Andrew E.
AU - Miller, Robert H.
AU - Brady-Kalnay, Susann M.
PY - 2009/9/1
Y1 - 2009/9/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=70149096641&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=70149096641&partnerID=8YFLogxK
U2 - 10.1158/0008-5472.CAN-09-0863
DO - 10.1158/0008-5472.CAN-09-0863
M3 - Article
C2 - 19690139
AN - SCOPUS:70149096641
SN - 0008-5472
VL - 69
SP - 6960
EP - 6968
JO - Cancer Research
JF - Cancer Research
IS - 17
ER -