The positive feedback between Snail and DAB2IP regulates EMT, invasion and metastasis in colorectal cancer.
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.
Department of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, Guangdong Province, People's Republic of China.|Department of Pathology, The Affiliated Hospital of Luzhou Medical College, Luzhou 646000, Luzhou, China.
Jianmei
J
Wang
Department of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, Guangdong Province, People's Republic of China.|Guangdong Province Key Laboratory of Molecular Tumor Pathology, Guangzhou 510515, Guangdong Province, People's Republic of China.
Xiaohui
X
Zhu
Department of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, Guangdong Province, People's Republic of China.|Guangdong Province Key Laboratory of Molecular Tumor Pathology, Guangzhou 510515, Guangdong Province, People's Republic of China.
Jinlong
J
Hu
Department of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, Guangdong Province, People's Republic of China.|Guangdong Province Key Laboratory of Molecular Tumor Pathology, Guangzhou 510515, Guangdong Province, People's Republic of China.
Guoyang
G
He
Department of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, Guangdong Province, People's Republic of China.|Guangdong Province Key Laboratory of Molecular Tumor Pathology, Guangzhou 510515, Guangdong Province, People's Republic of China.
Xiaomei
X
Li
Department of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, Guangdong Province, People's Republic of China.|Guangdong Province Key Laboratory of Molecular Tumor Pathology, Guangzhou 510515, Guangdong Province, People's Republic of China.
Pingxiang
P
Wu
Department of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, Guangdong Province, People's Republic of China.|Guangdong Province Key Laboratory of Molecular Tumor Pathology, Guangzhou 510515, Guangdong Province, People's Republic of China.
Xiaoli
X
Ren
Department of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, Guangdong Province, People's Republic of China.|Guangdong Province Key Laboratory of Molecular Tumor Pathology, Guangzhou 510515, Guangdong Province, People's Republic of China.
Feifei
F
Wang
Department of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, Guangdong Province, People's Republic of China.|Guangdong Province Key Laboratory of Molecular Tumor Pathology, Guangzhou 510515, Guangdong Province, People's Republic of China.
Wenting
W
Liao
Department of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, Guangdong Province, People's Republic of China.|Guangdong Province Key Laboratory of Molecular Tumor Pathology, Guangzhou 510515, Guangdong Province, People's Republic of China.
Li
L
Liang
Department of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, Guangdong Province, People's Republic of China.|Guangdong Province Key Laboratory of Molecular Tumor Pathology, Guangzhou 510515, Guangdong Province, People's Republic of China.
Yanqing
Y
Ding
D000818:Animals; D018938:Caco-2 Cells; D002277:Carcinoma / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015179:Colorectal Neoplasms / Q000378:metabolism*; D058750:Epithelial-Mesenchymal Transition; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D045325:HCT116 Cells; D019073:HT29 Cells; D006801:Humans; D047468:Immunoprecipitation; D051379:Mice; D008819:Mice, Nude; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D011379:Prognosis; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000378:metabolism*; D020703:ras GTPase-Activating Proteins / Q000378:metabolism*
C462952:DAB2IP protein, human; C561450:Dab2ip protein, mouse; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; D020703:ras GTPase-Activating Proteins
DAB2IP; Ezh2; Snail; colorectal carcinoma; metastasis