RT Journal Article
SR Electronic
T1 Girdin is a component of the lateral polarity protein network restricting cell dissemination
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 733329
DO 10.1101/733329
A1 Cornélia Biehler
A1 Li-Ting Wang
A1 Myriam Sévigny
A1 Alexandra Jetté
A1 Clémence Gamblin
A1 Rachel Catterall
A1 Élise Houssin
A1 Luke McCaffrey
A1 Patrick Laprise
YR 2019
UL http://biorxiv.org/content/early/2019/08/14/733329.abstract
AB 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 a 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.