Mechanotransduction and YAP-dependent matrix remodelling is required for the generation and maintenance of cancer-associated fibroblasts.
Mechanotransduction and YAP-dependent matrix remodelling is required for the generation and maintenance of cancer-associated fibroblasts.
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DOI：
10.1038/ncb2756
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发表时间：
2013-06
影响因子：
21.3
通讯作者：
中科院分区：
文献类型：
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为了更多地了解癌症相关成纤维细胞（CAF），我们从乳腺癌进展的不同阶段分离出成纤维细胞，并分析了它们的功能和基因表达。这些分析揭示了雅普转录因子的激活是CAFs的特征。CAF需要雅普功能来促进基质硬化、癌细胞侵袭和血管生成。ECM的重塑和癌细胞侵袭的促进需要肌动球蛋白细胞骨架。雅普调节几种细胞骨架调节因子的表达，包括ANLN和DIAPH 3，并控制MYL 9/MLC 2的蛋白水平。基质硬化进一步增强了雅普活化，从而建立了一个前馈自增强环，有助于维持CAF表型。肌动球蛋白收缩性和Src功能是刚性基质激活雅普所必需的。此外，瞬时ROCK抑制能够破坏前馈回路，导致CAF表型的持久逆转。
To learn more about cancer-associated fibroblasts (CAFs), we have isolated fibroblasts from different stages of breast cancer progression and analysed their function and gene expression. These analyses reveal that activation of the YAP transcription factor is a signature feature of CAFs. YAP function is required for CAFs to promote matrix stiffening, cancer cell invasion and angiogenesis. Remodelling of the ECM and promotion of cancer cell invasion requires the actomyosin cytoskeleton. YAP regulates the expression of several cytoskeletal regulators, including ANLN, and DIAPH3, and controls the protein levels of MYL9/MLC2. Matrix stiffening further enhances YAP activation, thus establishing a feed-forward self-reinforcing loop that helps to maintain the CAF phenotype. Actomyosin contractility and Src function are required for YAP activation by stiff matrices. Further, transient ROCK inhibition is able to disrupt the feed-forward loop leading to a long-lasting reversion of the CAF phenotype.
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影响因子：
16
作者：
Descot, Arnaud;Hoffmann, Reinhard;Posern, Guido
通讯作者：
Posern, Guido
影响因子：
7.5
作者：
Calvo, Fernando;Sahai, Erik
通讯作者：
Sahai, Erik
影响因子：
3.5
作者：
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通讯作者：
Charras, G. T.
影响因子：
64.5
作者：
Dong, Jixin;Feldmann, Georg;Pan, Duojia
通讯作者：
Pan, Duojia
影响因子：
21.3
作者：
通讯作者：
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