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.

Adipose tissue, obesity and adipokines: role in cancer promotion

“…The relation of visfatin to colorectal cancer (CRC) is among the best characterized to date [94][95][96], but data supporting its role in breast cancer or postmenopausal breast cancer (BC/PBC) is increasing [97]. Research also demonstrates a role of visfatin in ovarian cancers [98].…”

“…Specifically, CRC cells express chemokine receptors, CXCR4 and CXCR7, both of which can bind SDF-1 that promotes survival and migration of the cancerous cells [101,102]. Wen-Shih Huang et al [96] demonstrated that increased production of visfatin leads to increased expression of SDF-1. This is mediated by the B1 integrin and involves signaling through the ERK and p38 MAPK pathways [96].…”

“…Wen-Shih Huang et al [96] demonstrated that increased production of visfatin leads to increased expression of SDF-1. This is mediated by the B1 integrin and involves signaling through the ERK and p38 MAPK pathways [96]. ERK and p38 MAPK signaling lead to an increase in NF-KB and AP-1, leading to the increased expression of SDF-1 and increased CRC cell survival and migration [96].…”

“…This is mediated by the B1 integrin and involves signaling through the ERK and p38 MAPK pathways [96]. ERK and p38 MAPK signaling lead to an increase in NF-KB and AP-1, leading to the increased expression of SDF-1 and increased CRC cell survival and migration [96]. Inhibitors of NF-kB and AP-1 effectively decreased the expression of SDF-1 [96].…”

“…ERK and p38 MAPK signaling lead to an increase in NF-KB and AP-1, leading to the increased expression of SDF-1 and increased CRC cell survival and migration [96]. Inhibitors of NF-kB and AP-1 effectively decreased the expression of SDF-1 [96]. A third pathway recently identified involves redox pathways and the reduction of reactive oxygen metabolites by visfatin through increased activity of antioxidative enzymes superoxide dismutase (SOD), catalse (CAT), and glutathione peroxidase (GSHPx).…”