DCLK1 is up-regulated and associated with metastasis and prognosis in colorectal cancer
DCLK1 is up-regulated and associated with metastasis and prognosis in colorectal cancer
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DCLK1 上调并与结直肠癌的转移和预后相关。
DOI：
10.1007/s00432-016-2218-0
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发表时间：
2016-10-01
影响因子：
3.6
通讯作者：
An, Guangyu
中科院分区：
文献类型：
--
作者：
Gao, Tianbo;Wang, Min;An, Guangyu
转移是结直肠癌 (CRC) 相关死亡的主要原因，而癌症干细胞 (CSC) 被认为是引发转移行为的主要原因。最近发现双皮质素样激酶 1 (DCLK1) 是胃肠道 CSC 的标志物。在此，我们旨在通过临床和体外研究探讨DCLK1是否与CRC转移相关。分别通过定量RT-PCR和免疫组化染色分析人CRC组织中DCLK1 mRNA和蛋白的表达水平。选择人CRC细胞系SW480来探讨DCLK1过表达对细胞迁移和侵袭的影响。此外，还确定了DCLK1与上皮间质转化（EMT）之间的关联。与正常结直肠组织相比，DCLK1在人结直肠组织中表达显着上调，与患者的高淋巴转移和不良预后密切相关。 DCLK1 表达与 CRC 患者的总生存率呈负相关。 SW480细胞中DCLK1的过表达显着促进细胞迁移和侵袭。此外，我们验证了 DCLK1 可以通过上调 SW480 细胞中间质标记 Vimentin 和 ZEB1 以及下调上皮标记 E-cadherin 来促进癌细胞的 EMT。DCLK1 上调可能通过激活 EMT 在 CRC 转移和不良预后中发挥重要作用。 DCLK1 可作为 CRC 预后的独立预测因子。
Metastasis is a primary cause of colorectal cancer (CRC)-related death, and cancer stem cells (CSCs) are thought to be majorly responsible for initiating metastatic behaviors. Doublecortin-like kinase 1 (DCLK1) was recently discovered to be a marker for gastrointestinal CSCs. Here, we aimed to explore whether DCLK1 is associated with CRC metastasis through clinical and in vitro investigations.The expression levels of DCLK1 mRNA and protein in human CRC tissues were analyzed through quantitative RT-PCR and immunohistochemistry staining, respectively. Human CRC cell line SW480 was selected to explore the effect of DCLK1 overexpression on cell migration and invasion. Besides, the associations between DCLK1 and epithelial-mesenchymal transition (EMT) were determined.Compared to normal colorectal tissues, DCLK1 expression was significantly up-regulated in human CRC tissues and correlated well with high lymphatic metastasis and poor prognosis in patients. DCLK1 expression was inversely associated with overall survival in CRC patients. Overexpression of DCLK1 in SW480 cells markedly promoted cell migration and invasion. Furthermore, we validated that DCLK1 could facilitate EMT in cancer cells by up-regulation of the mesenchymal markers Vimentin and ZEB1 and down-regulation of the epithelial marker E-cadherin in SW480 cells.DCLK1 up-regulation may play a contributory role in CRC metastasis and poor prognosis via activation of EMT. DCLK1 may serve as an independent predictor for CRC prognosis.