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Moving on: Molecular mechanisms in TGFβ-induced epithelial cell migration

机译:进展:TGFβ诱导的上皮细胞迁移的分子机制

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摘要

TGFβ, particularly TGFβ1-3, has been shown to promote epithelial dedifferentiation or epithelial-mesenchymal transition (EMT). While inhibition of epithelial cell proliferation in response to TGFβ is mainly mediated by the well-characterised Smad-pathway and subsequent regulation of gene transcription, the molecular mechanisms leading to TGFβ-induced migration, invasion and metastasis of epithelial tumour cells are less clear. Recent results from several groups suggest that the gain of tumourigenic activity by TGFβ includes signalling by mitogen-activated protein kinases (MAP kinases), phosphatidylinositol 3-kinase (PI3-K) and Rho-GTPases. Activation of the MAP kinases extracellular signal-regulated kinase (ERK) 1 and 2, p38 as well as c-jun N-terminal kinase (JNK) has been identified as important steps in TGFβ-induced, Smad4-independent signal transduction in epithelial cells. A role of activated ERK and JNK and their association with focal complexes in TGFβ-induced cell migration and actin cytoskeleton reorganisation of carcinoma cells has been identified recently. In this review we will focus on new data about the molecular mechanisms involved in the TGFβ-induced Smad-independent regulation of epithelial cell migration.
机译:TGFβ,特别是TGFβ1-3,已显示出促进上皮去分化或上皮-间质转化(EMT)。尽管对TGFβ的应答抑制上皮细胞增殖主要是由特征明确的Smad途径和随后的基因转录调节介导的,但导致TGFβ诱导的上皮肿瘤细胞迁移,侵袭和转移的分子机制尚不清楚。来自几个研究小组的最新结果表明,TGFβ获得的致瘤尿活性包括有丝分裂原激活的蛋白激酶(MAP激酶),磷脂酰肌醇3-激酶(PI3-K)和Rho-GTPase的信号传导。 MAP激酶的激活胞外信号调节激酶(ERK)1和2,p38以及c-jun N末端激酶(JNK)已被确定为TGFβ诱导的上皮细胞Smad4独立信号转导的重要步骤。 。最近已经确定了活化的ERK和JNK及其与局灶复合物的关联在TGFβ诱导的癌细胞迁移和肌动蛋白细胞骨架重组中的作用。在这篇综述中,我们将重点关注有关TGFβ诱导的Smad依赖性上皮细胞迁移调节的分子机制的新数据。

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