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

Autor: Cornélia Biehler, Li-Ting Wang, Myriam Sévigny, Alexandra Jetté, Clémence L Gamblin, Rachel Catterall, Elise Houssin, Luke McCaffrey, Patrick Laprise
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Zdroj: PLoS Genetics, Vol 16, Iss 3, p e1008674 (2020)
Druh dokumentu: article
ISSN: 1553-7390
1553-7404
DOI: 10.1371/journal.pgen.1008674
Popis: 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.
Databáze: Directory of Open Access Journals
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