title: Visfatin is involved in promotion of colorectal carcinoma malignancy through an inducing EMT mechanism.
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.
authors.affiliation: School of Biomedical Sciences, Chengdu Medical College, Chengdu, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Yang
authors.affiliation: School of Biomedical Sciences, Chengdu Medical College, Chengdu, China.
authors.forename: Kun
authors.initials: K
authors.lastname: Zhang
authors.affiliation: School of Biomedical Sciences, Chengdu Medical College, Chengdu, China.
authors.forename: Haixing
authors.initials: H
authors.lastname: Song
authors.affiliation: School of Biomedical Sciences, Chengdu Medical College, Chengdu, China.
authors.forename: Mingbo
authors.initials: M
authors.lastname: Wu
authors.affiliation: School of Biomedical Sciences, Chengdu Medical College, Chengdu, China.
authors.forename: Jingyi
authors.initials: J
authors.lastname: Li
authors.affiliation: School of Pharmacy, Chengdu Medical College, Chengdu, China.
authors.forename: Ziyi
authors.initials: Z
authors.lastname: Yong
authors.affiliation: School of Basic Medical Sciences, Chengdu Medical College, Chengdu, China.
authors.forename: Sheng
authors.initials: S
authors.lastname: Jiang
authors.affiliation: Department of Pharmacology, Key Laboratory of Drug Targeting and Drug Delivery Systems, West China School of Pharmacy, Sichuan University, Sichuan, China.
authors.forename: Xi
authors.initials: X
authors.lastname: Kuang
authors.affiliation: School of Biomedical Sciences, Chengdu Medical College, Chengdu, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Zhang
mesh_terms: D001665:Binding Sites; D002277:Carcinoma / Q000235:genetics / Q000378:metabolism* / Q000401:mortality / Q000556:secondary; D002465:Cell Movement; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D016207:Cytokines / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D000071679:Glycogen Synthase Kinase 3 beta / Q000378:metabolism; D045325:HCT116 Cells; D006801:Humans; D053208:Kaplan-Meier Estimate; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D054409:Nicotinamide Phosphoribosyltransferase / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D058539:Phosphatidylinositol 3-Kinase / Q000378:metabolism; D010766:Phosphorylation; D011401:Promoter Regions, Genetic; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D034622:RNA Interference; D015398:Signal Transduction; D000071250:Snail Family Transcription Factors / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic; D014162:Transfection; D054875:Ubiquitination; D014746:Vimentin / Q000235:genetics / Q000378:metabolism; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism
chemical_list: C495270:CTNNB1 protein, human; D016207:Cytokines; D000071250:Snail Family Transcription Factors; D014746:Vimentin; D051176:beta Catenin; D054409:Nicotinamide Phosphoribosyltransferase; C085455:nicotinamide phosphoribosyltransferase, human; D058539:Phosphatidylinositol 3-Kinase; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; D051057:Proto-Oncogene Proteins c-akt
keywords: Akt/GSK-3β; EMT; Snail; colorectal cancer; visfatin