Peroxisome proliferator-activated receptor-gamma activation inhibits @entity5 XXXX by antagonizing @entity3078 -mediated epithelial-mesenchymal transition.

@entity3229 @entity137 @entity21043 @entity3111 @entity5 @entity641 @entity4506 @entity2 @entity4222 @entity19 @entity14570 @entity3078 @entity3 @entity6170 @entity3112
Epithelial-mesenchymal transition (EMT) was shown to confer @entity5 cells with abilities essential for @entity3 , including migratory phenotype, invasiveness, resistance to apoptosis, evading immune surveillance, and @entity5 stem cell traits. Therefore, inhibition of EMT can be an important therapeutic strategy to inhibit @entity5 @entity3 . Here, we show that activation of peroxisome proliferator-activated receptor y ( @entity3229 -y) inhibits @entity641 ( @entity641 )-induced EMT in @entity2 cells and prevents @entity3 by antagonizing @entity3078 function. Activation of @entity3229 -y by synthetic ligands ( @entity4506 and @entity6170 ) or by a constitutively active form of @entity3229 -y prevents @entity641 -induced loss of @entity3112 expression and inhibits the induction of mesenchymal markers ( @entity3111 , @entity21043 , fibronectin) and matrix metalloproteases. Consistently, activation of @entity3229 -y also inhibited EMT-induced @entity4222 and invasion of @entity2 cells. Furthermore, effects of @entity3229 -y ligands were attenuated by siRNA-mediated knockdown of @entity3229 -y, indicating that the ligand-induced responses are @entity3229 -y dependent. Selective knockdown of @entity14570 and @entity3078 by siRNA showed that @entity641 -induced EMT is @entity3078 dependent in @entity2 cells. Activation of @entity3229 -y inhibits @entity641 -induced Smad transcriptional activity but had no effect on the phosphorylation or nuclear translocation of Smads. Consistently, @entity3229 -y activation prevented @entity641 -induced transcriptional repression of @entity3112 promoter and inhibited transcriptional activation of @entity21043 promoter. Finally, treatment of @entity19 with @entity4506 or knockdown of @entity3078 in @entity5 cells significantly inhibited @entity641 -induced experimental @entity3 in SCID-Beige @entity19 . Together, with the low @entity137 profile of @entity3229 -y ligands, our data show that these ligands may serve as potential therapeutic agents to inhibit @entity3 .
