The positive feedback between Snail and DAB2IP regulates EMT, invasion and metastasis in colorectal cancer.
The positive feedback between Snail and DAB2IP regulates EMT, invasion and metastasis in colorectal cancer.
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snail和DAB2IP之间的正反馈调节结直肠癌的EMT、侵袭和转移
DOI：
10.18632/oncotarget.4861
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发表时间：
2015-09-29
期刊：
影响因子：
--
通讯作者：
Ding Y
中科院分区：
文献类型：
--
作者：
Wang J;Zhu X;Hu J;He G;Li X;Wu P;Ren X;Wang F;Liao W;Liang L;Ding Y
DAB 2 IP已被鉴定为几种癌症中的肿瘤抑制因子，但其在结直肠癌（CRC）进展中的致癌作用和转录调控机制仍不清楚。在本研究中，DAB 2 IP在结直肠癌组织中下调，并且是结直肠癌患者生存的有价值的预后标志物，特别是在晚期。此外，DAB 2 IP足以抑制CRC的增殖、上皮-间质转化（EMT）、侵袭和转移。在机械上，EZH 2/HDAC 1/Snail的线性复合物有助于CRC细胞中的DAB 2 IP沉默。本研究进一步证明了Snail与DAB 2 IP之间存在正反馈环，DAB 2 IP是Snail诱导的细胞攻击行为所必需的。大肠癌组织中DAB 2 IP与Snail和EZH 2表达呈负相关。我们的研究结果揭示了DAB 2 IP表达在CRC进展中的抑制作用和新的调节机制。DAB 2 IP可能是临床结直肠癌患者潜在的、新的治疗和预后靶点。
DAB2IP has been identified as a tumor suppressor in several cancers but its oncogenic role and transcriptionally regulatory mechanisms in the progression of colorectal carcinoma (CRC) remain unknown. In this study, DAB2IP was down-regulated in CRC tissues and a valuable prognostic marker for survival of CRC patients, especially in the late stage. Moreover, DAB2IP was sufficient to suppress proliferation, epithelial-mesenchymal transition (EMT), invasion and metastasis in CRC. Mechanically, the linear complex of EZH2/HDAC1/Snail contributed to DAB2IP silencing in CRC cells. The study further proved that the positive feedback loop between Snail and DAB2IP existed in CRC cells and DAB2IP was required for Snail-induced aggressive cell behaviors. Finally, DAB2IP correlated negatively with Snail and EZH2 expressions in CRC tissues. Our findings reveal the suppressive role and a novel regulatory mechanism of DAB2IP expression in the progression of CRC. DAB2IP may be a potential, novel therapeutic and prognostic target for clinical CRC patients.