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

نویسندگان

  • Yunyan Wu
  • Fuyuki Sato
  • Toshiyuki Yamada
  • Ujjal Kumar Bhawal
  • Takeshi Kawamoto
  • Katsumi Fujimoto
  • Mitsuhide Noshiro
  • Hiroko Seino
  • Satoko Morohashi
  • Kenichi Hakamada
  • Yoshimitsu Abiko
  • Yukio Kato
  • Hiroshi Kijima
چکیده

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.

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عنوان ژورنال:
  • International journal of oncology

دوره 41 4  شماره 

صفحات  -

تاریخ انتشار 2012