The positive feedback between Snail and DAB2IP regulates EMT, invasion and metastasis in colorectal cancer
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Jianmei Wang1,3,*, Xiaohui Zhu1,2,*, Jinlong Hu1,2, Guoyang He1,2, Xiaomei Li1,2, Pingxiang Wu1,2, Xiaoli Ren1,2, Feifei Wang1,2, Wenting Liao1,2, Li Liang1,2, Yanqing Ding1,2
1Department of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, Guangdong Province, People’s Republic of China
2Guangdong Province Key Laboratory of Molecular Tumor Pathology, Guangzhou 510515, Guangdong Province, People’s Republic of China
3Department of Pathology, The Affiliated Hospital of Luzhou Medical College, Luzhou 646000, Luzhou, China
*These authors have contributed equally to this work
Yanqing Ding, e-mail: [email protected]
Li Liang, e-mail: [email protected]
Keywords: DAB2IP, Ezh2, Snail, colorectal carcinoma, metastasis
Received: May 09, 2015 Accepted: August 11, 2015 Published: August 21, 2015
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.
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