Visfatin facilitates gastric cancer malignancy by targeting snai1 via the NF-κB signaling

Abstract

Background: Visfatin acts as an oncogenic factor in numerous tumors through a variety of cellular processes. Visfatin has been revealed to promote cell migration and invasion in gastric cancer (GC). Snai1 is a well-known regulator of EMT process in cancers. However, the relationship between visfatin and snai1 in GC remains unclear. The current study aimed to explore the role of visfatin in GC. Methods: The RT-qPCR and western blot analysis were used to measure RNA and protein levels, respectively. The cell migration and invasion were tested by Trans-well assays and western blot analysis. Results: Visfatin showed upregulation in GC cells. Additionally, Visfatin with increasing concentration facilitated epithelial-mesenchymal transition (EMT) process by increasing E-cadherin and reducing N-cadherin and Vimentin protein levels in GC cells. Moreover, endogenous overexpression and knockdown of visfatin promoted and inhibited migratory and invasive abilities of GC cells, respectively. Then, we found that snai1 protein level was positively regulated by visfatin in GC cells. In addition, visfatin activated the NF-κB signaling to modulate snai1 protein expression. Furthermore, the silencing of snai1 counteracted the promotive impact of visfatin on cell migration, invasion and EMT process in GC. Conclusion: Visfatin facilitates cell migration, invasion and EMT process by targeting snai1 via the NF-κB signaling, which provides a potential insight for the treatment of GC.

Visfatin Promotes the Metastatic Potential of Chondrosarcoma Cells by Stimulating AP-1-Dependent MMP-2 Production in the MAPK Pathway

“…Some research has reported that high levels of visfatin expression enhance NAD + production and increase the proliferation of colorectal cancer cells by activating the Wnt/β-catenin pathway [23]. In gastric cancer, visfatin facilitates cell migratory and invasive abilities, as well as the EMT process, by targeting the SNAIL transcription factor SNAI1 via NF-κB signaling [24]. Thus, visfatin is critical for tumor cell proliferation, migration, and survival [24,25], although the effects of visfatin in chondrosarcoma metastasis are uncertain.…”

“…In gastric cancer, visfatin facilitates cell migratory and invasive abilities, as well as the EMT process, by targeting the SNAIL transcription factor SNAI1 via NF-κB signaling [24]. Thus, visfatin is critical for tumor cell proliferation, migration, and survival [24,25], although the effects of visfatin in chondrosarcoma metastasis are uncertain. Our cellular and preclinical investigations found that visfatin reliably promotes chondrosarcoma metastasis.…”

Extracellular nicotinamide phosphoribosyltransferase: role in disease pathophysiology and as a biomarker

“…As demonstrated by Soncini et al (75), one of the mechanisms by which eNAMPT could promote cancer cell migration and metastasis is by inducing epithelial-tomesenchymal transition (EMT) via transforming growth factor b signaling. eNAMPT could also trigger EMT via NF-kB/Snail signaling, as shown by others (230,231). Additional mechanisms proposed to explain the pro-migratory and pro-invasive effects of eNAMPT are 1) the induction of matrix-degrading enzymes in cancer cells, such as MMP-2 and -9 gelatinases (214, 218,221,222,226,227,232) and 2) the stimulation of angiogenesis by inducing pro-angiogenic factors in endothelial cells (81) and cancer cells (222).…”

Adipokines as Regulators of Autophagy in Obesity-Linked Cancer

“…Although a specific receptor for visfatin has not been described, it has been shown to induce tumor cell proliferation by promoting cellular survival through NF-κB/Notch1, AKT/GSK-3β/β-catenin, c-Abl/STAT3, AKT/ERK1/2, and acetylated SIRT1/p53, and by promoting the G1 to S transition of the cell cycle [ 56 , 64 , 65 , 66 , 67 , 68 , 69 , 70 ]. Likewise, it promotes cell migration and invasion by inducing the expression of the NF-κB-dependent transcription factor Snai1 [ 71 , 72 ]. Additionally, visfatin increases MMP-2 secretion through the ERK activation-mediated transcription factor AP-1 [ 67 ] and the promotion of EMT by enhancing the expression of mesenchymal markers (N-cadherin, ZEB1, and vimentin) [ 71 ].…”

“…Likewise, it promotes cell migration and invasion by inducing the expression of the NF-κB-dependent transcription factor Snai1 [ 71 , 72 ]. Additionally, visfatin increases MMP-2 secretion through the ERK activation-mediated transcription factor AP-1 [ 67 ] and the promotion of EMT by enhancing the expression of mesenchymal markers (N-cadherin, ZEB1, and vimentin) [ 71 ].…”