Girdin is a component of the lateral polarity protein network restricting cell dissemination
Autoři:
Cornélia Biehler aff001; Li-Ting Wang aff003; Myriam Sévigny aff001; Alexandra Jetté aff001; Clémence L. Gamblin aff001; Rachel Catterall aff003; Elise Houssin aff001; Luke McCaffrey aff003; Patrick Laprise aff001
Působiště autorů:
Centre de Recherche sur le Cancer, Universitaire de Québec-UL, Québec, Canada
aff001; Centre de Recherche sur le Cancer, Université Laval, Québec, Canada
aff001; axe oncologie du Centre de Recherche du Centre Hospitalier, Universitaire de Québec-UL, Québec, Canada
aff002; Rosalind and Morris Goodman Cancer Research Centre, McGill University, Montreal, Canada
aff003; Gerald Bronfman Department of Oncology, McGill University, Montreal, Canada
aff004
Vyšlo v časopise:
Girdin is a component of the lateral polarity protein network restricting cell dissemination. PLoS Genet 16(3): e32767. doi:10.1371/journal.pgen.1008674
Kategorie:
Research Article
doi:
https://doi.org/10.1371/journal.pgen.1008674
Souhrn
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.
Klíčová slova:
Caco-2 cells – Cell polarity – Confocal microscopy – Cytoskeletal proteins – Drosophila melanogaster – Embryos – Epithelial cells – Morphogenesis
Zdroje
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