Sp1 is required for transforming growth factor-beta-induced mesenchymal transition and migration in pancreatic cancer cells.
Transition from a sessile epithelial phenotype to a migrating mesenchymal phenotype is a crucial step in transforming growth factor-beta (TGF-beta)-induced pancreatic cancer cell migration and invasion. These profound morphologic and functional alterations are associated with characteristic changes in TGF-beta-regulated gene expression, defined by rapid repression of epithelial markers and a strong and sustained transcriptional induction of mesenchymal markers such as the intermediate filament vimentin. In this study, we have analyzed the role of the transcription factor Sp1 in TGF-beta-induced and Smad-mediated gene regulation during epithelial to mesenchymal transition (EMT) and migration of pancreatic cancer cells. Here, we show that Sp1 is required for TGF-beta-induced EMT, and that this function is especially mediated through transcriptional induction of vimentin. Our results emphasize the functional relevance of vimentin in TGF-beta-induced EMT because prevention of its induction strongly reduces cell migration. Altogether, this study helps to better understand the role of Sp1 in TGF-beta-induced progression of pancreatic cancer. It suggests that Sp1, via transcriptional induction of vimentin, cooperates with activated Smad complexes in mesenchymal transition and migration of pancreatic cancer cells upon TGF-beta stimulation.
Jungert
Kerstin
K
Department of Gastroenterology, University of Ulm, 35043 Ulm, Germany.
Buck
Anita
A
von Wichert
Götz
G
Adler
Guido
G
König
Alexander
A
Buchholz
Malte
M
Gress
Thomas M
TM
Ellenrieder
Volker
V
D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008648:Mesoderm / Q000473:pathology; D010190:Pancreatic Neoplasms / Q000139:chemically induced / Q000235:genetics / Q000473:pathology*; D011401:Promoter Regions, Genetic; D034741:RNA, Small Interfering / Q000235:genetics; D016329:Sp1 Transcription Factor / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D014162:Transfection; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D014746:Vimentin / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism
D034741:RNA, Small Interfering; D016329:Sp1 Transcription Factor; D016212:Transforming Growth Factor beta; D014746:Vimentin