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PTEN is required for the migration and invasion of Ras-transformed MDCK cells

Lu Yan1, Kazuya Tsujita1,2, Yasuyuki Fujita3,4

  • 1Division of Membrane Biology, Department of Biochemistry and Molecular Biology, Kobe University Graduate School of Medicine, Japan.

FEBS Letters
|February 4, 2021
PubMed

Insights

The phosphatase and tensin homolog deleted on chromosome 10 (PTEN) tumor suppressor is crucial for epithelial cancer cell invasion. Loss of PTEN impairs cell migration, but its membrane recruitment at the cell rear is vital for invasion.

Area of Science:

  • Cell Biology
  • Cancer Research
  • Molecular Biology

Background:

  • Phosphoinositide balance in the plasma membrane regulates actin polymerization and cell migration.
  • Oncogenic transformations, involving PI3K and PTEN, are linked to cancer cell metastasis.
  • PTEN acts as a tumor suppressor, influencing cell behavior.

Purpose of the Study:

  • To investigate the role of the PTEN tumor suppressor gene in epithelial cancer cell invasion.
  • To determine how PTEN loss affects cancer cell migration and invasion phenotypes.
  • To elucidate the mechanism of PTEN's function in cell invasion, focusing on its membrane recruitment.

Main Methods:

  • Utilized Ras-transformed MDCK cells to study PTEN's role in invasion.
  • Assessed cell migratory phenotype in collagen gel.
  • Quantified invasion through Matrigel.
  • Conducted rescue experiments to examine PTEN's C2 domain-mediated membrane recruitment.

Main Results:

  • Loss of PTEN significantly suppressed the migratory and invasive capabilities of epithelial cancer cells.
  • PTEN's C2 domain-mediated membrane recruitment, particularly at the rear of cells, was essential for invasion.
  • PTEN functions to suppress leading edge formation, thereby regulating efficient cancer cell migration.

Conclusions:

  • PTEN is a critical suppressor of epithelial cancer cell invasion.
  • The localization and membrane recruitment of PTEN are key to its tumor-suppressive function in cell migration.
  • Targeting PTEN's role in regulating cell polarity and migration may offer therapeutic strategies for cancer metastasis.
Keywords:
PI3KPTENRascancer cell invasion

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