The BHLH transcription factor DEC1 plays an important role in the epithelial-mesenchymal transition of pancreatic cancer
The BHLH transcription factor DEC1 plays an important role in the epithelial-mesenchymal transition of pancreatic cancer
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DOI：
10.3892/ijo.2012.1559
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发表时间：
2012-10-01
影响因子：
5.2
通讯作者：
Kijima, Hiroshi
中科院分区：
文献类型：
--
作者：
Wu, Yunyan;Sato, Fuyuki;Kijima, Hiroshi
DEC1 (BHLHE40/Stra13/Sharp2) 是一种碱性螺旋-环-螺旋 (bHLH) 转录因子，参与细胞凋亡和细胞增殖的调节以及对缺氧的反应。上皮间质转化（EMT）是导致多种肿瘤细胞侵袭和迁移的重要步骤，TGF-β治疗已被证明可以诱导癌细胞发生EMT。然而，. DEC1 在 TGF-β 诱导的 EMT 中的重要性仍不清楚。我们研究了 DEC1 在 PANC-1 细胞（一种人类胰腺癌细胞系）EMT 中的作用。结果，我们发现PANC-1细胞中DEC1被TGF-β上调，并调节EMT相关因子的表达和核、细胞质或膜定位的水平，包括磷酸化Smad3（pSmad3）、snail、claudin-4和N-cadherin。在 TGF-β 存在的情况下，通过 siRNA 敲低 DEC1 可抑制 EMT 过程中的形态变化，而 TGF-β 则诱导 PANC-1 细胞呈现纺锤形形态。此外，DEC1表达与TGF-β的联合治疗与PANC-1细胞的迁移和侵袭密切相关。免疫组织化学显示，在胰腺癌组织中检测到DEC1和pSmad3，而与邻近的非癌胰腺组织相比，癌组织中claudin-4的表达较弱。这些发现表明 DEC1 在胰腺癌中这些 EMT 相关因子的调节中发挥着重要作用。
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.