A role for Id in the regulation of TGF-β-induced epithelial-mesenchymal transdifferentiation
A role for Id in the regulation of TGF-β-induced epithelial-mesenchymal transdifferentiation
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DOI：
10.1038/sj.cdd.4401467
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发表时间：
2004-10-01
影响因子：
12.4
通讯作者：
Miyazono, K
中科院分区：
文献类型：
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作者：
Kondo, M;Cubillo, E;Miyazono, K
上皮-间质转分化（EMT）是胚胎发育和各种上皮肿瘤进展过程中发生的重要形态发生事件。在小鼠NMuMG乳腺上皮细胞中，转化生长因子（TGF）-β可诱导EMT。在这里，我们证明了螺旋-环-螺旋因子，E2 A和分化抑制剂（Id）蛋白在TGF-β诱导的EMT中的核心作用。异位表达E2 A的上皮细胞采用成纤维细胞表型并获得迁移/侵袭特性，伴随着E-钙粘蛋白表达的抑制。Id蛋白与E2 A蛋白相互作用并拮抗E2 A依赖的E-钙粘蛋白启动子抑制。TGF-β显著降低Id蛋白的水平。此外，过度表达Id 2的NMuMG细胞对TGF-β诱导的EMT表现出部分抗性。因此，Id蛋白抑制E2 A蛋白对E-钙粘蛋白表达的作用，但在TGF-β刺激后，E2 A蛋白以比Id蛋白摩尔过量的量存在，从而超越它们的抑制功能并导致EMT。
Epithelial-mesenchymal transdifferentiation (EMT) is a critical morphogenic event that occurs during embryonic development and during the progression of various epithelial tumors. EMT can be induced by transforming growth factor (TGF)-beta in mouse NMuMG mammary epithelial cells. Here, we demonstrate a central role of helix-loop-helix factors, E2A and inhibitor of differentiation (Id) proteins, in TGF-beta-induced EMT. Epithelial cells ectopically expressing E2A adopt a fibroblastic phenotype and acquire migratory/invasive properties, concomitant with the suppression of E-cadherin expression. Id proteins interacted with E2A proteins and antagonized E2A-dependent suppression of the E-cadherin promoter. Levels of Id proteins were dramatically decreased by TGF-beta. Moreover, NMuMG cells overexpressed Id2 showed partial resistance to TGF-beta-induced EMT. Id proteins thus inhibit the action of E2A proteins on the expression of E-cadherin, but after TGF-beta stimulation, E2A proteins are present in molar excess of the Id proteins, thus over-riding their inhibitory function and leading to EMT.