Paracrine and autocrine signals induce and maintain mesenchymal and stem cell states in the breast.
Paracrine and autocrine signals induce and maintain mesenchymal and stem cell states in the breast.
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DOI：
10.1016/j.cell.2011.04.029
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发表时间：
2011-06-10
期刊：
影响因子：
64.5
通讯作者：
Weinberg RA
中科院分区：
文献类型：
--
作者：
Scheel C;Eaton EN;Li SH;Chaffer CL;Reinhardt F;Kah KJ;Bell G;Guo W;Rubin J;Richardson AL;Weinberg RA
上皮-间质转化（EMT）与运动性、侵袭性和自我更新特性的获得有关。在正常发育和肿瘤发病过程中，这种细胞表型的变化是由上皮细胞从其微环境接收的上下文信号诱导的。负责诱发EMT和维持由此产生的细胞状态的信号一直不清楚。我们描述了三种信号通路，包括转化生长因子(TGF)-β以及典型和非典型Wnt信号，它们共同诱导EMT程序的激活，然后以自分泌方式发挥作用以维持所产生的间质状态。下调上皮细胞中内源性合成的自分泌信号抑制剂可以诱导EMT程序。相反，通过添加这些途径的抑制剂破坏自分泌信号会抑制原发乳腺上皮细胞的迁移和自我更新，并抑制其转化衍生物的致瘤性和转移。
The epithelial-mesenchymal transition (EMT) has been associated with the acquisition of motility, invasiveness and self-renewal traits. During both normal development and tumor pathogenesis this change in cell phenotype is induced by contextual signals that epithelial cells receive from their microenvironment. The signals that are responsible for inducing an EMT and maintaining the resulting cellular state have been unclear. We describe three signaling pathways, involving Transforming Growth Factor (TGF)-β as well as canonical and non-canonical Wnt signaling, that collaborate to induce activation of the EMT program and thereafter function in an autocrine fashion to maintain the resulting mesenchymal state. Downregulation of endogenously synthesized inhibitors of autocrine signals in epithelial cells enables the induction of the EMT program. Conversely, disruption of autocrine signaling by added inhibitors of these pathways inhibits migration and self-renewal in primary mammary epithelial cells, and inhibits tumorigenicity and metastasis by their transformed derivatives.
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影响因子：
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