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首页> 外文期刊>Oncogene >Spreds, inhibitors of the Ras|[sol]|ERK signal transduction, are dysregulated in human hepatocellular carcinoma and linked to the malignant phenotype of tumors
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Spreds, inhibitors of the Ras|[sol]|ERK signal transduction, are dysregulated in human hepatocellular carcinoma and linked to the malignant phenotype of tumors

机译：Spres，Ras | [sol] | ERK信号转导的抑制剂，在人类肝细胞癌中失调，并与肿瘤的恶性表型有关。

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Aberrant activation of the Ras/Raf-1/extracellular-regulated kinase (ERK) pathway has been shown to be involved in the progression of human hepatocellular carcinoma (HCC). However, the mechanism of dysregulation of ERK activation is poorly understood. Recently, we identified Sprouty-related protein with Ena/vasodilator-stimulated phosphoprotein homology-1 domain (Spred) as a physiological inhibitor of the Ras/Raf-1/ERK pathway. In this study, we found that the expression levels of Spred-1 and -2 in human HCC tissue were frequently decreased, comparing with those in adjacent non-tumorous tissue. Moreover, Spred expression levels in HCC tissue were inversely correlated with the incidence of tumor invasion and metastasis. Forced expression of Spred-1 inhibited HCC cell proliferation in vitro and in vivo, which was associated with reduced ERK activation. Spred-1 overexpression also reduced the secretion of matrix metalloproteinase-9 (MMP-9) and MMP-2, which play important roles in tumor invasion and metastasis. In addition, Spred-1 inhibited growth factor-mediated HCC cell motility. These data indicate that the reduction of Spred expression in HCC is one of the causes of the acquisition of malignant features. Thus, Spred could be not only a novel prognostic factor but also a new therapeutic target for human HCC.
机译：Ras / Raf-1 /细胞外调节激酶（ERK）途径的异常激活已被证明与人类肝细胞癌（HCC）的进展有关。但是，ERK激活失调的机制了解甚少。最近，我们发现Ena /血管扩张剂刺激的磷蛋白同源性1域（Spred）的Sprouty相关蛋白是Ras / Raf-1 / ERK途径的生理抑制剂。在这项研究中，我们发现与邻近的非肿瘤组织相比，人HCC组织中Spred-1和-2的表达水平经常降低。此外，HCC组织中的Spred表达水平与肿瘤侵袭和转移的发生率呈负相关。 Spred-1的强制表达在体外和体内抑制HCC细胞增殖，这与ERK激活减少有关。 Spred-1过表达还减少了基质金属蛋白酶9（MMP-9）和MMP-2的分泌，它们在肿瘤的侵袭和转移中起着重要的作用。此外，Spred-1抑制生长因子介导的HCC细胞运动。这些数据表明，HCC中Spred表达的降低是获得恶性特征的原因之一。因此，Spred不仅可能是人类HCC的新预后因素，而且还是新的治疗靶标。

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