Girdin is a component of the lateral polarity protein network restricting cell dissemination

Cornélia Biehler1,2, Li-Ting Wang3, Myriam Sévigny1,2

  • 1Centre de Recherche sur le Cancer, Université Laval, Québec, Canada.

Plos Genetics
|March 21, 2020
PubMed

Insights

Girdin protein maintains epithelial cell polarity by inhibiting a kinase, preventing cancer progression. Loss of Girdin leads to cell dissemination and is linked to poor survival in breast and lung cancers.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Cancer Research

Background:

  • Epithelial cell polarity is crucial for tissue function.
  • Defects in cell polarity are linked to cancer progression.
  • Understanding polarity protein networks is essential.

Purpose of the Study:

  • To investigate the role of Girdin in epithelial cell polarity.
  • To determine the functional interactions of Girdin within the polarity protein network.
  • To explore Girdin's potential as a therapeutic target in epithelial cancers.

Main Methods:

  • Utilized Drosophila melanogaster as a model organism.
  • Investigated the interaction between Girdin and apical kinase aPKC.
  • Analyzed GIRDIN expression in human cancer subtypes.
  • Observed cell cyst and tumorsphere morphology and dissemination.

Main Results:

  • Drosophila Girdin and human GIRDIN inhibit the apical kinase aPKC, sustaining lateral polarity proteins.
  • Loss of GIRDIN causes disorganized cell cysts and promotes cell dissemination.
  • Altered GIRDIN expression correlates with poor survival in breast and lung cancers.
  • GIRDIN preserves epithelial structure and restricts cell dissemination.

Conclusions:

  • A core mechanism for epithelial cell polarization from flies to humans involving GIRDIN was discovered.
  • GIRDIN plays a vital role in maintaining epithelial integrity and cell cohesion.
  • GIRDIN has potential as a therapeutic target to inhibit epithelial cancer progression.

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