YAP-independent mechanotransduction drives breast cancer progression

Joanna Y. Lee, Jessica K. Chang, Antonia A. Dominguez, Hong-pyo Lee, Sungmin Nam, Julie Chang, Sushama Varma, Lei S. Qi, Robert B. West and Ovijit Chaudhuri ()
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Joanna Y. Lee: Stanford University
Jessica K. Chang: Department of Genetics, Stanford University School of Medicine
Antonia A. Dominguez: Stanford University
Hong-pyo Lee: Stanford University
Sungmin Nam: Stanford University
Julie Chang: Stanford University
Sushama Varma: Stanford University School of Medicine
Lei S. Qi: Stanford University
Robert B. West: Stanford University School of Medicine
Ovijit Chaudhuri: Stanford University

Nature Communications, 2019, vol. 10, issue 1, 1-9

Abstract: Abstract 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.

Date: 2019
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DOI: 10.1038/s41467-019-09755-0

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