Visit our Expo - Redox and Inflammation signaling 2012

Session XVII : Cell signaling in health and disease Poster XVII, 32
Implication of TRIP6, a novel molecular partner of the MAGI-1b scaffolding molecule
in invasiveness
Larissa Kotelevets1, Erik Bruyneel3, Alexei Kruglov1,4, Marc Bracke3, Frans van Roy2
and Eric Chastre1
1 INSERM U683, Faculté de Médecine X. Bichat, Paris, France
2 Department for Molecular Biomedical Research, VIB-Ghent University, B-9052 Ghent
3 Laboratory of Experimental Cancerology, Ghent University Hospital, B-9000 Ghent,
Belgium
4 Institute of Theoretical and Experimental Biophysics, Russian Academy of Sciences,
Pushchino, Russia.
We recently established the critical role of the PTEN/MAGI-1b signalosome in the
stabilization of cell-cell contacts and the suppression of invasiveness. The PTEN tumor
suppressor is recruited to E-cadherin junctional complexes through the binding to the 2nd
PDZ domain of the MAGI-1b scaffolding molecule, whereas #-catenin interacts with the 5th
PDZ domain of MAGI-1b (Kotelevets et al, FASEB J 19,115,2005). To identify additional
effector molecules that might regulate the activity and the composition of the PTEN / MAGI-
1b complexes, we used yeast-two hybrid screening. Among the clones identified, we focused
on TRIP6 (Thyroid Receptor Interacting Protein 6)/ZRP-1 (Zyxin-related Protein 1). TRIP6
has been reported to associate with p130Cas in focal adhesion complexes. We demonstrated
that TRIP6 interacted directly with MAGI-1b through binding to the 5th PDZ-binding motif.
Ectopic expression of TRIP6 induced invasiveness in the epithelial kidney MDCK and
MDCKts-src cells in a PI3-kinase dependant manner, and reverted the E-cadherin-dependent
cell-cell aggregation. In this connection, we observed a slight increase in AKT activity in
MDCKts-src derivatives transfected with TRIP6 expression vectors, compared to parental
cells. The TRIP6Stop473 mutant, lacking the PDZ binding motif was unable to promote cell
invasiveness and did not interfere with cell-cell aggregation. The competing peptides
corresponding to the C-terminus of TRIP6 or b-catenin promoted invasiveness in TRIP6
Stop473-transfected MDCKts-src cells but not in the parental cell line. These results suggest
that TRIP6-induced invasiveness in epithelial cells involves the induction of cell motility by
the TRIP6 core molecule, whereas the C-terminus is required to destabilizes E-cadherin
junctional complexes by competing with #-catenin for the interaction with MAGI-1b.
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