Functional relevance of a six mesenchymal gene signature in epithelial-mesenchymal transition (EMT) reversal by the triple angiokinase inhibitor, XXXX ( @entity9815 ).

@entity43 @entity9815 @entity137 @entity73112 @entity5962 @entity189 @entity18075 @entity73110 @entity2277 @entity73111 @entity16445
UNASSIGNED: Epithelial-mesenchymal transition (EMT), a crucial mechanism in @entity189 progression, describes the process whereby epithelial cells lose their apico-basal polarity and junctional complexes and acquire a mesenchymal-like morphology. Several markers are considered to be authentic indicators of an epithelial or mesenchymal status; however, there is currently no comprehensive or systematic method with which to determine their functional relevance. Previously, we identified a 33-gene EMT signature comprising 25 epithelial and 6 mesenchymal genes that best describe this concept of the EMT spectrum. Here, we designed small-scale siRNA screens targeting these six mesenchymal signature genes ( @entity73110 , @entity73111 , @entity16445 , @entity73112 , @entity2277 , @entity18075 ) to explore their functional relevance and their roles during EMT reversal by @entity9815 ( @entity9815 ) in a mesenchymal-like SKOV3 @entity43 cell line. We found that neither cell proliferation nor @entity137 was affected by silencing any of these genes. SKOV3 cells expressing siRNA against mesenchymal genes ( @entity18075 , @entity73111 , @entity73110 , @entity16445 , and @entity73112 ) showed enhanced colony compaction (reduced inter-nuclear distance). Inductions of @entity5962 expression were only observed in @entity73112 - and @entity18075 -silenced SKOV3 cells. In addition, only @entity73112 -silenced SKOV3 cells showed increased anoikis. Finally, we identified that @entity73112 and @entity18075 were down-regulated in @entity9815 -treated SKOV3 cells and @entity73112 - and @entity18075 -silenced SKOV3 cells showed enhanced @entity9815 -induced up-regulation of @entity5962 . @entity9815 -treated SKOV3 cells also showed colony compaction and decreases in EMT scores both in vitro and in vivo. We conclude that @entity73112 and @entity18075 are functionally relevant in EMT reversal. This study thus provides a proof-of-concept for the use of in vitro siRNA screening to explore the EMT-related functions of selected genes and their potential relevance in the discovery of EMT reversing drugs.
