The BHLH transcription factor DEC1 plays an important role in the epithelial-mesenchymal transition of pancreatic cancer

被引:62
作者
Wu, Yunyan [1 ,2 ,3 ]
Sato, Fuyuki [1 ]
Yamada, Toshiyuki [4 ]
Bhawal, Ujjal Kumar [5 ]
Kawamoto, Takeshi [6 ]
Fujimoto, Katsumi [6 ]
Noshiro, Mtsuhide [6 ]
Seino, Hiroko [1 ]
Morohashi, Satoko [1 ]
Hakamada, Kenichi [7 ]
Abiko, Yoshimitsu [5 ]
Kato, Yukio [6 ]
Kijima, Hiroshi [1 ]
机构
[1] Hirosaki Univ, Grad Sch Med, Dept Pathol & Biosci, Hirosaki, Aomori 0368562, Japan
[2] China Med Univ, Dept Pathol, Affiliated Hosp 1, Shenyang 110001, Peoples R China
[3] China Med Univ, Coll Basic Med Sci, Shenyang 110001, Peoples R China
[4] Hirosaki Univ, Grad Sch Med, Dept Biochem & Genome Biol, Hirosaki, Aomori 0368562, Japan
[5] Nihon Univ, Sch Dent Matsudo, Dept Biochem & Mol Biol, Chiba 2718587, Japan
[6] Hiroshima Univ, Grad Sch Biomed Sci, Dept Dent & Med Biochem, Hiroshima 7348553, Japan
[7] Hirosaki Univ, Grad Sch Med, Dept Gastrointestinal Surg, Hirosaki, Aomori 0368562, Japan
关键词
differentiated embryonic chondrocyte gene 1; epithelial-mesenchymal transition; transforming growth factor-beta; human pancreatic cancer; TGF-BETA; CLAUDIN-1; EXPRESSION; E-CADHERIN; CELLS; ACTIVATION; LOOP; PROTEIN; STRA13; SNAIL; GENE;
D O I
10.3892/ijo.2012.1559
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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-beta treatment has been shown to induce cancer cells to undergo EMT. However, the. significance of DEC1 in TGF-beta-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-beta 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-beta, DEC1 knockdown by siRNA inhibited morphological changes during EMT processes, while TGF-beta induced PANC-1 cells to taken on a spindle-shaped morphology. Furthermore, a combination treatment of DEC1 expression with TGF-beta 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.
引用
收藏
页码:1337 / 1346
页数:10
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