title: Visfatin induces stromal cell-derived factor-1 expression by β1 integrin signaling in colorectal cancer cells.
abstract: Obesity has been shown to be associated with the risk of colorectal cancer (CRC). Adipokines produced by the adipose tissue are linked to some malignancies, including CRC. Visfatin is an adipokine shown to be a biomarker of CRC malignant potential. In addition, the stromal cell-derived factor-1 (SDF-1) has been reported to play a role in CRC progression. Although the relationship between visfatin and CRC has been established, the underlying mechanism has not been clarified. We investigated the molecular mechanism governing the interaction between visfatin stimulation and SDF-1 expression in human CRC cell lines. We found that visfatin stimulation led to an increase in the expression and secretion of SDF-1 in CRC DLD-1 and SW48 cells. Experiments involving specific inhibitors and small interfering RNA demonstrated that the activation of ERK and p38 mitogen-activated protein kinase (MAPK) pathways are critical for visfatin-induced SDF-1 expression. Analysis of transcription factor binding using ELISA and luciferase reporter assays revealed that visfatin increased NF-κB- and AP-1-DNA-binding activities in DLD-1 cells. Inhibition of NF-κB and AP-1 activation blocked the visfatin-induced expression and activity of the SDF-1 promoter. The effect of visfatin on DLD-1 signaling and SDF-1 expression was mediated by β1 integrin. In summary, these findings provide novel insights pertaining to the pathophysiological role of visfatin in CRC.
authors.affiliation: Division of Colon and Rectal Surgery, Department of Surgery, Chang Gung Memorial Hospital, Chiayi, Taiwan.
authors.forename: Wen-Shih
authors.initials: WS
authors.lastname: Huang
authors.forename: Cheng-Nan
authors.initials: CN
authors.lastname: Chen
authors.forename: Chun-I
authors.initials: CI
authors.lastname: Sze
authors.forename: Chih-Chuan
authors.initials: CC
authors.lastname: Teng
mesh_terms: D054392:Adipokines / Q000378:metabolism; D000273:Adipose Tissue / Q000378:metabolism; D045744:Cell Line, Tumor; D054377:Chemokine CXCL12 / Q000235:genetics / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D019012:Integrin beta1 / Q000235:genetics / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000235:genetics; D016328:NF-kappa B; D054409:Nicotinamide Phosphoribosyltransferase / Q000378:metabolism / Q000494:pharmacology*; D018808:Transcription Factor AP-1 / Q000032:analysis
chemical_list: D054392:Adipokines; D054377:Chemokine CXCL12; D019012:Integrin beta1; D016328:NF-kappa B; D018808:Transcription Factor AP-1; D054409:Nicotinamide Phosphoribosyltransferase