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Updated: Dec 25, 2025

Analyzing the Function of Small GTPases by Microinjection of Plasmids into Polarized Epithelial Cells
Published on: May 31, 2011
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.
Abstract:
Epithelial cell polarity defects support cancer progression. It is thus crucial to decipher the functional interactions within the polarity protein network. Here we show that Drosophila Girdin and its human ortholog (GIRDIN) sustain the function of crucial lateral polarity proteins by inhibiting the apical kinase aPKC. Loss of GIRDIN expression is also associated with overgrowth of disorganized cell cysts. Moreover, we observed cell dissemination from GIRDIN knockdown cysts and tumorspheres, thereby showing that GIRDIN supports the cohesion of multicellular epithelial structures. Consistent with these observations, alteration of GIRDIN expression is associated with poor overall survival in subtypes of breast and lung cancers. Overall, we discovered a core mechanism contributing to epithelial cell polarization from flies to humans. Our data also indicate that GIRDIN has the potential to impair the progression of epithelial cancers by preserving cell polarity and restricting cell dissemination.
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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