YAP-independent mechanotransduction drives breast cancer progression
YAP-independent mechanotransduction drives breast cancer progression
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DOI：
10.1038/s41467-019-09755-0
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发表时间：
2019-04-23
影响因子：
16.6
通讯作者：
Chaudhuri, Ovijit
中科院分区：
文献类型：
--
作者：
Lee, Joanna Y.;Chang, Jessica K.;Chaudhuri, Ovijit
组织硬度增加是乳腺癌进展的驱动因素。转录调节因子雅普被认为是一种通用的机械传感器，主要是基于二维培养研究。然而，雅普在体内乳腺癌中的作用仍不清楚。在这里，我们发现，机械转导发生独立的雅普在乳腺癌患者样本和机械可调的三维文化。从机制上讲，3D培养和体内雅普活性的缺乏与应力纤维的缺乏以及相对于2D培养细胞核横截面积的数量级减少有关。这项工作突出了雅普在机械转导中的上下文依赖性作用，并确定雅普不介导乳腺癌中的机械转导。
Increased tissue stiffness is a driver of breast cancer progression. The transcriptional regulator YAP is considered a universal mechanotransducer, based largely on 2D culture studies. However, the role of YAP during in vivo breast cancer remains unclear. Here, we find that mechanotransduction occurs independently of YAP in breast cancer patient samples and mechanically tunable 3D cultures. Mechanistically, the lack of YAP activity in 3D culture and in vivo is associated with the absence of stress fibers and an order of magnitude decrease in nuclear cross-sectional area relative to 2D culture. This work highlights the context-dependent role of YAP in mechanotransduction, and establishes that YAP does not mediate mechanotransduction in breast cancer.