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.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Adaptor Proteins, Signal Transducing / genetics
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Adaptor Proteins, Signal Transducing / metabolism*
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Breast / pathology
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Breast Density
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Breast Neoplasms / pathology*
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Carcinoma, Intraductal, Noninfiltrating / pathology*
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Cell Culture Techniques / methods
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Cell Line, Tumor
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Disease Progression
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Extracellular Matrix / metabolism
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Extracellular Matrix / pathology*
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Female
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Gene Knockout Techniques
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HEK293 Cells
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Humans
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Mechanotransduction, Cellular*
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Neoplasm Invasiveness / pathology
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Phosphoproteins / genetics
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Phosphoproteins / metabolism*
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Transcription Factors
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YAP-Signaling Proteins
Substances
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Adaptor Proteins, Signal Transducing
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Phosphoproteins
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Transcription Factors
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YAP-Signaling Proteins
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YAP1 protein, human