PI3K/AKT-mediated upregulation of WDR5 promotes colorectal cancer metastasis by directly targeting ZNF407.
PI3K/AKT-mediated upregulation of WDR5 promotes colorectal cancer metastasis by directly targeting ZNF407.
复制标题
PI3K/AKT介导的WDR5上调通过直接靶向ZNF407促进结直肠癌转移
DOI：
10.1038/cddis.2017.111
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发表时间：
2017-03-16
影响因子：
9
通讯作者：
Huang W
中科院分区：
文献类型：
--
作者：
Tan X;Chen S;Wu J;Lin J;Pan C;Ying X;Pan Z;Qiu L;Liu R;Geng R;Huang W
结直肠癌（CRC）是癌症死亡的第三大常见原因，并且具有高的肝和肺转移率。然而，远处转移是晚期结直肠癌治疗的主要障碍，导致生存率极低。在这项研究中，我们确定了WDR 5，一个调节脊椎动物发育和细胞自我更新和重编程的重要因子，作为CRC患者的新预后标志物和治疗靶点。我们证明WDR 5在CRC组织中上调，并在体外和体内促进CRC转移。为了研究WDR 5对CRC细胞命运的影响，我们用生长因子和抑制剂处理CRC细胞。我们报道了WDR 5是一种新的CRC转移因子，其通过响应PI 3 K/AKT信号通路触发上皮-间质转化（EMT）过程。此外，WDR 5显示直接与ZNF 407启动子结合，调节细胞EMT过程，导致CRC转移。因此，我们的研究结果强烈地将WDR 5定位为CRC的有价值的标志物，抑制WDR 5或相关的信号通路可能是未来开发抗CRC治疗的有效策略。
Colorectal cancer (CRC) is the third most common cause of cancer deaths, and has a high rate of liver and lung metastasis. Unfortunately, distant metastasis is the main barrier for advanced CRC therapy and leads to a very low survival rate. In this study, we identified WDR5, a vital factor that regulates vertebrate development and cell self-renewal and reprogramming, as a novel prognostic marker and therapeutic target for CRC patients. We demonstrate that WDR5 is upregulated in CRC tissues and promotes CRC metastasis both in vitro and in vivo. In an effort to investigate the impact of WDR5 on CRC cell fate, we treated CRC cells with growth factor and inhibitor. We report that WDR5 is a novel factor in the metastasis of CRC by triggering epithelial–mesenchymal transition (EMT) process in response to the PI3K/AKT signaling pathway. Moreover, WDR5 shows a direct binding to the ZNF407 promoter on regulating cellular EMT process, leading to CRC metastasis. Hence, our findings strongly position WDR5 as a valuable marker for CRC, and inhibiting WDR5 or the associated signaling pathways may be an effective strategy for the future development of anti-CRC therapy.