The positive feedback between Snail and DAB2IP regulates EMT, invasion and metastasis in colorectal cancer

// Jianmei Wang 1, 3, * , Xiaohui Zhu 1, 2, * , Jinlong Hu 1, 2 , Guoyang He 1, 2 , Xiaomei Li 1, 2 , Pingxiang Wu 1, 2 , Xiaoli Ren 1, 2 , Feifei Wang 1, 2 , Wenting Liao 1, 2 , Li Liang 1, 2 , Yanqing Ding 1, 2 1 Department of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, Guangdong Province, People’s Republic of China 2 Guangdong Province Key Laboratory of Molecular Tumor Pathology, Guangzhou 510515, Guangdong Province, People’s Republic of China 3 Department of Pathology, The Affiliated Hospital of Luzhou Medical College, Luzhou 646000, Luzhou, China * These authors have contributed equally to this work Correspondence to: Yanqing Ding, e-mail: dyq@fimmu.com Li Liang, e-mail: redsnow007@hotmail.com Keywords: DAB2IP, Ezh2, Snail, colorectal carcinoma, metastasis Received: May 09, 2015      Accepted: August 11, 2015      Published: August 21, 2015 ABSTRACT 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.