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首页> 外文期刊>Journal of Cellular Physiology >Visfatin induces stromal cell-derived factor-1 expression by ??1 integrin signaling in colorectal cancer cells
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Visfatin induces stromal cell-derived factor-1 expression by ??1 integrin signaling in colorectal cancer cells

机译:Visfatin诱导基质细胞衍生因子- 1表达式由? ?结直肠癌细胞

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摘要

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-??B- and AP-1-DNA-binding activities in DLD-1 cells. Inhibition of NF-??B 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 ??1 integrin. In summary, these findings provide novel insights pertaining to the pathophysiological role of visfatin in CRC. J. Cell. Physiol. ? 2012 Wiley Periodicals, Inc.
机译:肥胖已被证明是相关的结直肠癌(CRC)的风险。由脂肪组织一些有关恶性肿瘤,包括CRC。adipokine CRC的生物标志物恶性潜能。细胞衍生因子- 1 (SDF-1)已经被报道在CRC进展中发挥作用。visfatin和CRC之间的关系没有建立,底层机制被澄清。管理之间的互动机制visfatin刺激和SDF-1表达式人类的CRC细胞系。刺激导致增加表达式和分泌的CRC DLD-1 SDF-1 SW48细胞。和小干扰RNA证明了激活ERK和p38增殖作用蛋白激酶(MAPK)途径至关重要visfatin-induced SDF-1表达式。用ELISA和转录因子绑定荧光素酶化验显示visfatin记者增加了NF - ? ?在DLD-1细胞。激活了visfatin-inducedSDF-1启动子的表达和活动。visfatin DLD-1信号和的影响SDF-1表达式是由? ?总结,这些发现提供了新颖的见解有关的病理生理作用visfatin CRC。期刊、公司。

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