PTK7 regulates Id1 expression in CD44-high glioma cells

Neuro Oncol. 2015 Apr;17(4):505-15. doi: 10.1093/neuonc/nou227. Epub 2014 Sep 8.


Background: CD44 is a molecular marker associated with molecular subtype and treatment resistance in glioma. More effective therapies will result from approaches aimed at targeting the CD44-high gliomas.

Methods: Protein tyrosine kinase 7 (PTK7) mRNA expression was analyzed based on The Cancer Genome Atlas glioblastoma dataset. PTK7 expression was depleted through lentivirus-mediated short hairpin RNA knockdown. Terminal deoxynucleotidyl transferase dUTP nick-end labeling was used to evaluate cell apoptosis following PTK7 knockdown. Gene expression analysis was performed on Affymetrix microarray. A nude mice orthotopic tumor model was used to evaluate the in vivo effect of PTK7 depletion.

Results: PTK7 is highly expressed in CD44-high glioblastoma and predicts unfavorable prognosis. PTK7 knockdown attenuated cell proliferation, impaired tumorigenic potential, and induced apoptosis in CD44-high glioma cell lines. Gene expression analysis identified inhibitor of DNA Binding 1 (Id1) gene as a potential downstream effector for PTK7. Overexpression of Id1 mostly restored the cell proliferation and colony formation attenuated by PTK7 depletion. PTK7 enhanced anchorage-independent growth in normal human astrocytes, which was attenuated by Id1 knockdown. Furthermore, PTK7 regulated Id1 expression through modulating TGF-β/Smad signaling, while pharmacological inhibition on TGF-β/Smad signaling or PTK7/Id1 depletion attenuated TGF-β-stimulated cell proliferation. PTK7 depletion consistently reduced Id1 expression, suppressed tumor growth, and induced apoptosis in a murine orthotopic tumor model, which could be translated into prolonged survival in tumor-bearing mice.

Conclusions: PTK7 regulates Id1 expression in CD44-high glioma cell lines. Targeting PTK7 could be an effective strategy for treating glioma with high CD44 expression.

Keywords: CD44; PTK7; cell proliferation; glioma; tumorigenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies
  • Apoptosis
  • Biomarkers
  • Brain Neoplasms / enzymology
  • Brain Neoplasms / metabolism*
  • Cell Adhesion Molecules / immunology
  • Cell Adhesion Molecules / metabolism*
  • Cell Line, Tumor
  • Cell Proliferation
  • Gene Expression
  • Glioblastoma / enzymology
  • Glioblastoma / metabolism*
  • Humans
  • Hyaluronan Receptors / immunology
  • Hyaluronan Receptors / metabolism*
  • Inhibitor of Differentiation Protein 1 / metabolism*
  • Kaplan-Meier Estimate
  • Mice
  • Mice, Nude
  • Prognosis
  • Receptor Protein-Tyrosine Kinases / immunology
  • Receptor Protein-Tyrosine Kinases / metabolism*
  • Signal Transduction


  • Antibodies
  • Biomarkers
  • CD44 protein, human
  • Cell Adhesion Molecules
  • Hyaluronan Receptors
  • ID1 protein, human
  • Inhibitor of Differentiation Protein 1
  • PTK7 protein, human
  • Receptor Protein-Tyrosine Kinases