Macrophage migration inhibitory factor engages PI3K/Akt signalling and is a prognostic factor in metastatic melanoma.
Macrophage migration inhibitory factor engages PI3K/Akt signalling and is a prognostic factor in metastatic melanoma.
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巨噬细胞迁移抑制因子参与PI3K/AKT信号传导，并且是转移性黑色素瘤的预后因素。
DOI：
10.1186/1471-2407-14-630
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发表时间：
2014-08-29
期刊：
影响因子：
3.8
通讯作者：
Thorne RF
中科院分区：
文献类型：
--
作者：
Oliveira CS;de Bock CE;Molloy TJ;Sadeqzadeh E;Geng XY;Hersey P;Zhang XD;Thorne RF
巨噬细胞移动抑制因子（Macrophage migration inhibitor factor，MIF）是一种广泛表达的细胞因子，参与细胞周期调控和增殖控制等多种细胞过程。在许多癌症类型中已经报道了MIF的过表达，并且先前已经表明MIF在黑素细胞肿瘤中上调，其中最高表达水平发生在恶性黑色素瘤中。然而，MIF在黑色素瘤中高表达的临床意义尚未见报道。使用siRNA介导的基因敲低在人黑素瘤细胞系中耗尽MIF表达，并且使用增殖、细胞周期、凋亡、克隆形成和Akt信号传导的体外测定来监测效果。表达微阵列数据的计算机分析用于使用单变量考克斯回归模型将黑素瘤肿瘤中的MIF表达水平与患者总体存活率相关联。MIF的敲低显著降低增殖，增加凋亡和减少锚定非依赖性生长。其作用与进入S期的细胞数量减少、细胞周期蛋白D1和CDK 4表达降低、p27表达增加和Akt磷酸化降低相关。临床结果数据分析显示，原发性黑色素瘤中MIF表达水平与结果无关（HR = 1.091，p = 0.892），而转移性病变中MIF水平较高与疾病进展较快显著相关（两项独立研究中分别为HR = 2.946，p = 0.003和HR = 4.600，p = 0.004）。我们的体外分析表明，在人类黑色素瘤细胞系中，MIF在PI 3 K/Akt通路的上游起作用。此外，耗尽的MIF抑制黑色素瘤增殖，活力和克隆形成能力。临床上，转移性黑色素瘤中的高MIF水平被发现与更快的疾病复发相关。这些发现支持了MIF信号在黑色素瘤中的临床意义，并为靶向和监测MIF在临床黑色素瘤中的表达提供了强有力的理论基础。本文的在线版本（doi：10.1186/1471-2407-14-630）包含补充材料，可供授权用户使用。
Macrophage migration inhibitory factor (MIF) is a widely expressed cytokine involved in a variety of cellular processes including cell cycle regulation and the control of proliferation. Overexpression of MIF has been reported in a number of cancer types and it has previously been shown that MIF is upregulated in melanocytic tumours with the highest expression levels occurring in malignant melanoma. However, the clinical significance of high MIF expression in melanoma has not been reported. MIF expression was depleted in human melanoma cell lines using siRNA-mediated gene knockdown and effects monitored using in vitro assays of proliferation, cell cycle, apoptosis, clonogenicity and Akt signalling. In silico analyses of expression microarray data were used to correlate MIF expression levels in melanoma tumours with overall patient survival using a univariate Cox regression model. Knockdown of MIF significantly decreased proliferation, increased apoptosis and decreased anchorage-independent growth. Effects were associated with reduced numbers of cells entering S phase concomitant with decreased cyclin D1 and CDK4 expression, increased p27 expression and decreased Akt phosphorylation. Analysis of clinical outcome data showed that MIF expression levels in primary melanoma were not associated with outcome (HR = 1.091, p = 0.892) whereas higher levels of MIF in metastatic lesions were significantly associated with faster disease progression (HR = 2.946, p = 0.003 and HR = 4.600, p = 0.004, respectively in two independent studies). Our in vitro analyses show that MIF functions upstream of the PI3K/Akt pathway in human melanoma cell lines. Moreover, depletion of MIF inhibited melanoma proliferation, viability and clonogenic capacity. Clinically, high MIF levels in metastatic melanoma were found to be associated with faster disease recurrence. These findings support the clinical significance of MIF signalling in melanoma and provide a strong rationale for both targeting and monitoring MIF expression in clinical melanoma. The online version of this article (doi:10.1186/1471-2407-14-630) contains supplementary material, which is available to authorized users.
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影响因子：
5.8
作者：
Guo Y;Hou J;Luo Y;Wang D
通讯作者：
Wang D
DOI：
10.1073/pnas.56.1.72
发表时间：
1966-01-01
影响因子：
11.1
作者：
DAVID, JR
通讯作者：
DAVID, JR
影响因子：
5.2
作者：
Culp, W. David;Tsagozis, Panagiotis;Garland, Donita
通讯作者：
Garland, Donita
影响因子：
4.2
作者：
Baron, Nina;Deuster, Oliver;Bacher, Michael
通讯作者：
Bacher, Michael
巨噬细胞是巨噬细胞迁移抑制因子的重要且以前未被认可的来源。
影响因子：
15.3
作者：
Calandra, Thierry;Bernhagen, Juergen;Mitchell, Robert A.;Bucala, Richard
通讯作者：
Bucala, Richard