Absence of DAB2IP promotes cancer stem cell like signatures and indicates poor survival outcome in colorectal cancer.

ABSTRACT: Metastasis is a critical factor for the high mortality of colorectal cancer (CRC), but its mechanism is not completely understood. Epithelial-mesenchymal transition (EMT) is thought to play a key role in metastasis and also increases the cancer stem cell (CSC) feature that facilitates metastatic colonization. In this study, we investigated the biological roles of DAB2IP regulating EMT and stem cell-like features in human CRC. We demonstrate that DAB2IP suppresses NF-?B-mediated EMT and CSC features in CRC cells. In DAB2IP knockout mice, we discovered the hyperplasia in colonic epithelium which aberrantly represents the mesenchymal feature and NF-?B pathway activation. In clinic CRC tissue, we also reveal that reduced DAB2IP can enrich the CD133(+) subpopulation. DAB2IP expression was inversely correlated with tumor differentiation and metastasis, and patients with lower DAB2IP expression had shorter overall survival time. Taken together, our study demonstrates that DAB2IP inhibits NF-?B-inducing EMT and CSC to suppress the CRC progression, and also suggests that DAB2IP is a beneficial prediction factor for CRC patient prognosis.

SUBMITTER: Min J 

PROVIDER: S-EPMC4643237 | biostudies-literature | 2015 Nov

REPOSITORIES: biostudies-literature