Common activation of canonical Wnt signaling in pancreatic adenocarcinoma.
Common activation of canonical Wnt signaling in pancreatic adenocarcinoma.
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DOI：
10.1371/journal.pone.0001155
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发表时间：
2007-11-07
期刊：
影响因子：
3.7
通讯作者：
Hebrok M
中科院分区：
文献类型：
--
作者：
Pasca di Magliano M;Biankin AV;Heiser PW;Cano DA;Gutierrez PJ;Deramaudt T;Segara D;Dawson AC;Kench JG;Henshall SM;Sutherland RL;Dlugosz A;Rustgi AK;Hebrok M
胰腺导管腺癌是一种侵袭性极强的恶性肿瘤，预后极差。Kras基因的激活突变在绝大多数人PDA中是常见的。此外，最近的研究表明，胚胎信号通路如Hedgehog和Notch在这种疾病中不适当地上调。另一个胚胎信号通路，即经典Wnt级联的作用，仍然是有争议的。在这里，我们使用基因阵列分析作为一个平台，以证明在人类PDA的Wnt通路的典型臂的一般激活。此外，我们提供了胰腺癌小鼠模型中Wnt激活的证据。我们的研究结果还表明，Wnt信号可能被激活下游的刺猬信号，这是一个早期事件的PDA进化。Wnt抑制可阻断培养的腺癌细胞的增殖并诱导其凋亡，从而为开发胰腺癌Wnt抑制的新治疗策略提供证据。
Pancreatic ductal adenocarcinoma (PDA) is an extremely aggressive malignancy, which carries a dismal prognosis. Activating mutations of the Kras gene are common to the vast majority of human PDA. In addition, recent studies have demonstrated that embryonic signaling pathway such as Hedgehog and Notch are inappropriately upregulated in this disease. The role of another embryonic signaling pathway, namely the canonical Wnt cascade, is still controversial. Here, we use gene array analysis as a platform to demonstrate general activation of the canonical arm of the Wnt pathway in human PDA. Furthermore, we provide evidence for Wnt activation in mouse models of pancreatic cancer. Our results also indicate that Wnt signaling might be activated downstream of Hedgehog signaling, which is an early event in PDA evolution. Wnt inhibition blocked proliferation and induced apoptosis of cultured adenocarcinoma cells, thereby providing evidence to support the development of novel therapeutical strategies for Wnt inhibition in pancreatic adenocarcinoma.
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