title: The BHLH transcription factor DEC1 plays an important role in the epithelial-mesenchymal transition of pancreatic cancer.
abstract: DEC1 (BHLHE40/Stra13/Sharp2) is a basic helix-loop-helix (bHLH) transcription factor that is involved in the regulation of apoptosis and cell proliferation and the response to hypoxia. Epithelial-mesenchymal transition (EMT) is an important step leading to invasion and migration of various tumor cells, and TGF-β treatment has been shown to induce cancer cells to undergo EMT. However, the significance of DEC1 in TGF-β-induced EMT remains unknown. We examined the role of DEC1 in EMT of PANC-1 cells, a human pancreatic cancer cell line. As a result, we found that DEC1 was upregulated by TGF-β in PANC-1 cells, and regulated the expression and the levels of nuclear, cytoplasmic or membrane localization of EMT-related factors, including phosphorylated Smad3 (pSmad3), snail, claudin-4 and N-cadherin. In the presence of TGF-β, DEC1 knockdown by siRNA inhibited morphological changes during EMT processes, while TGF-β induced PANC-1 cells to taken on a spindle-shaped morphology. Furthermore, a combination treatment of DEC1 expression with TGF-β was closely linked to the migration and invasion of PANC-1 cells. Immunohistochemically, DEC1 and pSmad3 were detected within pancreatic cancer tissues, whereas claudin-4 expression was weaker in the cancer tissues compared with the adjacent non-cancer pancreatic tissues. These findings suggest that DEC1 plays an important role in the regulation of these EMT-related factors in pancreatic cancer.
authors: Department of Pathology and Bioscience, Hirosaki University Graduate School of Medicine, Hirosaki 036-8562, Japan.
authors: Yunyan
authors: Y
authors: Wu
authors: Fuyuki
authors: F
authors: Sato
authors: Toshiyuki
authors: T
authors: Yamada
authors: Ujjal Kumar
authors: UK
authors: Bhawal
authors: Takeshi
authors: T
authors: Kawamoto
authors: Katsumi
authors: K
authors: Fujimoto
authors: Mitsuhide
authors: M
authors: Noshiro
authors: Hiroko
authors: H
authors: Seino
authors: Satoko
authors: S
authors: Morohashi
authors: Kenichi
authors: K
authors: Hakamada
authors: Yoshimitsu
authors: Y
authors: Abiko
authors: Yukio
authors: Y
authors: Kato
authors: Hiroshi
authors: H
authors: Kijima
mesh_terms: D017209:Apoptosis; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D062506:Claudin-4 / Q000378:metabolism; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D034741:RNA, Small Interfering / Q000235:genetics; D051900:Smad3 Protein / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000096:biosynthesis / Q000235:genetics*
chemical_list: D062506:Claudin-4; C403671:DELEC1 protein, human; D034741:RNA, Small Interfering; C497790:SMAD3 protein, human; D051900:Smad3 Protein; D016212:Transforming Growth Factor beta; D025521:Tumor Suppressor Proteins