Up-regulation of sonic hedgehog contributes to XXXX -induced epithelial to mesenchymal transition in @entity1149 cells.

@entity72692 @entity146 @entity5 @entity1149 @entity2 @entity5962 @entity18075 @entity2533 @entity4851 @entity361
BACKGROUND: @entity2 , especially @entity1149 ( @entity1149 ) is the major cause of @entity5 in the United States. The @entity146 of @entity1149 has been shown to be associated with the acquisition of @entity361 ( @entity361 ). The acquisition of @entity361 phenotype induced by @entity2533 in several @entity5 cells has been implicated in @entity146 and resistance to conventional therapeutics; however, the molecular mechanism of @entity361 and @entity146 in @entity1149 remains unknown. METHODOLOGY/PRINCIPAL FINDINGS: In this study we found for the first time that the induction of @entity361 by chronic exposure of A549 @entity1149 cells to @entity2533 ( @entity72692 cells) led to the up-regulation of sonic hedgehog ( @entity4851 ) both at the mRNA and protein levels causing activation of hedgehog signaling. These results were also reproduced in another @entity1149 cell line (H2030). Induction of @entity361 was found to be consistent with aggressive characteristics such as increased clonogenic growth, cell motility and invasion. The @entity146 of these cells was attenuated by the treatment of A549-M cells with pharmacological inhibitors of Hh signaling in addition to @entity4851 knock-down by siRNA. The inhibition of Hh signaling by pharmacological inhibitors led to the reversal of @entity361 phenotype as confirmed by the reduction of mesenchymal markers such as @entity18075 and Fibronectin, and induction of epithelial marker @entity5962 . In addition, knock-down of @entity4851 by siRNA significantly attenuated @entity361 induction by @entity2533 . CONCLUSIONS/SIGNIFICANCE: Our results show for the first time the transcriptional up-regulation of @entity4851 by @entity2533 , which is mechanistically associated with @entity2533 induced @entity361 phenotype and aggressive behavior of @entity1149 cells. Thus the inhibitors of @entity4851 signaling could be useful for the reversal of @entity361 phenotype, which would inhibit the metastatic potential of @entity1149 cells and also make these @entity5 more sensitive to conventional therapeutics.
