Visfatin is involved in promotion of colorectal carcinoma malignancy through an inducing EMT mechanism

// Jing Yang 1, * , Kun Zhang 1, * , Haixing Song 1, * , Mingbo Wu 1, * , Jingyi Li 1 , Ziyi Yong 2 , Sheng Jiang 3 , Xi Kuang 4 , Tao Zhang 1 1 School of Biomedical Sciences, Chengdu Medical College, Chengdu, China 2 School of Pharmacy, Chengdu Medical College, Chengdu, China 3 School of Basic Medical Sciences, Chengdu Medical College, Chengdu, China 4 Department of Pharmacology, Key Laboratory of Drug Targeting and Drug Delivery Systems, West China School of Pharmacy, Sichuan University, Sichuan, China * These authors have contributed equally to this work Correspondence to: Xi Kuang, email: kuangxi56@163.com Tao Zhang, email: ztbillcmc@163.com Keywords: visfatin, colorectal cancer, EMT, Snail, Akt/GSK-3β Received: December 10, 2015      Accepted: March 28, 2016      Published: April 6, 2016 ABSTRACT Increasing evidences suggested visfatin, a newly discovered obesity-induced adipocytokine, is involved in promotion of cancer malignancy and correlated with worse clinical prognosis. While its effects and mechanisms on progression of colorectal cancer (CRC) remain unclear. Our clinical data show that visfatin protein is over expressed, positive associated with lymph node metastasis, high-grade tumor, and poor prognosis in 87 CRC patients. The levels of plasma visfatin are significantly upregulated in Stage IV colon cancer. Visfatin can significantly promote the in vitro migration and invasion of CRC cells via induction epithelial mesenchymal transition (EMT). It can increase the expression and nuclear translocation of Snail, a key transcription factor in regulating EMT. While silencing of Snail attenuates visfatin induced EMT. Further studies reveal visfatin can inhibit the association of Snail with GSK-3β and subsequently suppress ubiquitylation of Snail. In addition, visfatin can increase the expression and nuclear translocation of β-catenin, elevate its binding with Snail promoter, and then increase the transcription of Snail. While inhibitor of PI3K/Akt, LY294002, abolishes visfatin induced up regulation of Snail, Vimentin (Vim), β-catenin, and phosphorylated GSK-3β. In summary, our data suggest that increased expression of visfatin are associated with a more aggressive phenotype of CRC patients. It can trigger the EMT of CRC cells via Akt/GSK-3β/β-catenin signals.