DCLK1 promotes epithelial-mesenchymal transition via the PI3K/Akt/NF-κB pathway in colorectal cancer (Retracted Article)
DCLK1 promotes epithelial-mesenchymal transition via the PI3K/Akt/NF-κB pathway in colorectal cancer (Retracted Article)
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DOI：
10.1002/ijc.31232
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发表时间：
2018-05-15
影响因子：
6.4
通讯作者：
Tang, Hua
中科院分区：
文献类型：
--
作者：
Liu, Weiying;Wang, Shixing;Tang, Hua
双重皮质醇样激酶1(DCLK1)在结直肠癌上皮-间充质转化(EMT)过程中发挥重要作用。然而，DCLK1在调节结直肠癌EMT中的作用仍然知之甚少。在这项研究中，我们报道了DCLK1作为一个强大的癌基因在CRC细胞中以依赖于NF-kappa B的方式驱动其极端恶性的EMT特征的证据。机制研究表明，在大肠癌细胞EMT过程中，DCLK1通过PI3K/Akt/Sp1轴诱导NF-kappa Bp65亚基表达，并通过PI3K/Akt/I kappa Bα途径激活NF-kappa Bp65。此外，我们还发现沉默DCLK1的表达抑制了结直肠癌细胞的体内侵袭和转移。总之，我们的发现确定DCLK1是结直肠癌EMT轴的关键调节因子，从而暗示DCLK1是结直肠癌转移的潜在治疗靶点。
Double cortin-like kinase 1 (DCLK1) plays important roles during the epithelial-mesenchymal transition (EMT) process in human colorectal cancer (CRC). However, the role of DCLK1 in regulating the EMT of CRC is still poorly understood. In this study, we report evidence that DCLK1 acts as a potent oncogene to drive its extremely malignant character of EMT in an NF-kappa B-dependent manner in CRC cells. Mechanistic investigations showed that DCLK1 induced the NF-kappa Bp65 subunit expression through the PI3K/Akt/Sp1 axis and activated NF-kappa Bp65 through the PI3K/Akt/I kappa B alpha pathway during the EMT of CRC cells. Moreover, we found that silencing the expression of DCLK1 inhibited the invasion and metastasis of CRC cells in vivo. Collectively, our findings identify DCLK1 as a pivotal regulator of an EMT axis in CRC, thus implicating DCLK1 as a potential therapeutic target for CRC metastasis.