FOXO3 is essential for CD44 expression in pancreatic cancer cells
FOXO3 is essential for CD44 expression in pancreatic cancer cells
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DOI：
10.1038/onc.2016.426
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发表时间：
2017-05-11
期刊：
影响因子：
8
通讯作者：
Tachibana, H.
中科院分区：
文献类型：
--
作者：
Kumazoe, M.;Takai, M.;Tachibana, H.
胰腺导管腺癌（PDAC）是最致命的癌症类型之一，5年生存率仅为5%。一些研究表明，癌症干细胞（CSCs）被认为与复发和转移有关，因此建立靶向CSCs的方法至关重要。在这里，我们已经证明，环磷酸鸟苷（cGMP）抑制CD44的表达和PDAC中CSC的特性。微阵列分析表明，cGMP抑制Forkhead box O3（FOXO 3），这是一种肿瘤抑制因子。令人惊讶的是，我们的数据表明，FOXO 3是至关重要的CD44的表达和CSC的属性。我们的数据还表明，具有高FOXO 3激活特征的患者具有较差的预后。这一证据表明，cGMP诱导和FOXO 3抑制可能是胰腺CSC的理想候选物。
Pancreatic ductal adenocarcinoma (PDAC) is one of the most fatal types of cancer and the 5-year survival rate is only 5%. Several studies have suggested that cancer stem cells (CSCs) are thought to be involved in recurrence and metastasis and so it is essential to establish an approach targeting CSCs. Here we have demonstrated that cyclic guanosine monophosphate (cGMP) suppressed CD44 expression and the properties of CSCs in PDAC. Microarray analysis suggested that cGMP inhibited Forkhead box O3 (FOXO3), which is known as a tumor suppressor. Surprisingly, our data demonstrated that FOXO3 is essential for CD44 expression and the properties of CSCs. Our data also indicated that patients with high FOXO3 activation signatures had poor prognoses. This evidence suggested that cGMP induction and FOXO3 inhibition could be ideal candidates for pancreatic CSC.