Abstract:
:In multicellular epithelial tissues, the orientation of polarity of each cell must be coordinated. Previously, we reported that for Madin-Darby canine kidney cells in three-dimensional collagen gel culture, blockade of beta1-integrin by the AIIB2 antibody or expression of dominant-negative Rac1N17 led to an inversion of polarity, such that the apical surfaces of the cells were misorientated towards the extracellular matrix. Here, we show that this process results from the activation of RhoA. Knockdown of RhoA by short hairpin RNA reverses the inverted orientation of polarity, resulting in normal cysts. Inhibition of RhoA downstream effectors, Rho kinase (ROCK I) and myosin II, has similar effects. We conclude that the RhoA-ROCK I-myosin II pathway controls the inversion of orientation of epithelial polarity caused by AIIB2 or Rac1N17. These results might be relevant to the hyperactivation of RhoA and disruption of normal polarity frequently observed in human epithelial cancers.
journal_name
EMBO Repjournal_title
EMBO reportsauthors
Yu W,Shewan AM,Brakeman P,Eastburn DJ,Datta A,Bryant DM,Fan QW,Weiss WA,Zegers MM,Mostov KEdoi
10.1038/embor.2008.135subject
Has Abstractpub_date
2008-09-01 00:00:00pages
923-9issue
9eissn
1469-221Xissn
1469-3178pii
embor2008135journal_volume
9pub_type
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