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Protein-tyrosine pseudokinase 7 (PTK7) directs cancer cell motility and metastasis

Vladislav S Golubkov1, Natalie L Prigozhina2, Yong Zhang3

  • 1From the Sanford-Burnham Medical Research Institute, La Jolla, California 92037, vgolubkov@sanfordburnham.org.

The Journal of Biological Chemistry
|July 10, 2014
PubMed

Insights

Protein tyrosine kinase 7 (PTK7) expression and proteolysis are crucial for cancer cell motility and metastasis. Both factors, not just PTK7 levels, drive directional cell movement and spread in cancer.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Cancer Research

Background:

  • Widely expressed Protein tyrosine kinase 7 (PTK7) is vital for vertebrate tissue morphogenesis.
  • PTK7's function in cancer is modulated by proteases like MT1-MMP, ADAMs, and γ-secretase.

Purpose of the Study:

  • To investigate how full-length PTK7 and its cleavage site mutants influence cell motility in 2D and 3D environments.
  • To determine the relationship between PTK7 expression, proteolysis, and cell protrusion dynamics in cancer cells.
  • To evaluate the role of PTK7 in cancer metastasis using animal models and human tissue analysis.

Main Methods:

  • Utilized PTK7 mutants with varying MT1-MMP cleavage site functionality.
  • Assessed cell motility in 2D and 3D culture systems.
  • Analyzed cell protrusion structures (lamellipodia, invadopodia) and PTK7 proteolysis.
  • Employed mouse and chick embryo metastasis models with PTK7 overexpression and knock-out.
  • Examined PTK7 proteolysis in human colorectal cancer tissues.

Main Results:

  • PTK7 mutants differentially regulated cell motility based on the environment.
  • PTK7 expression and proteolysis correlated with cell protrusion dynamics in polarized cancer cells.
  • Both PTK7 overexpression and knock-out abrogated metastatic dissemination in animal models.
  • Intensive PTK7 proteolysis was observed in human colorectal tumors but not normal tissue.

Conclusions:

  • PTK7 expression and proteolysis are key determinants of directional cell motility and cancer metastasis.
  • The interplay between PTK7 levels and its proteolytic processing is critical for metastatic potential.
  • Targeting PTK7 proteolysis may offer a therapeutic strategy for inhibiting cancer spread.
Keywords:
CancerCell PolarityMatrix Metalloproteinase (MMP)MetastasisMigrationProtein Kinase

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