Matrix stiffness modulates YAP activation to control the drug resistance of breast cancer cells
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Department of Biophysics,School of Life Science and Technology,University of Electronic Science and Technology of China

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R 318.01

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    Abstract:

    Objective: To investigate the detailed molecular mechanism of matrix stiffness regulating cell drug resistance. Methods: Polyacrylamide hydrogels of soft substrate (10 kPa), hard substrate (38 kPa) and rigid substrate (57 kPa) with different matrix stiffness were configured to mimic the physical matrix stiffness at different stages of breast cancer in vivo. Results: (1) The cell proliferation rate on the hard substrate was significantly higher than that of the soft and rigid substrates. (2) The intracellular endocytosis was significantly lower on the hard substrate. (3) The YAP nucleus translocation increased significantly on the hard substrate, compared with soft and rigid substrates, indicating that YAP is a key molecule involved in the drug resistance of tumor cells. Conclusions: Matrix stiffness can regulate the drug resistance of breast cancer cells through YAP activation. This study not only provides a new direction for elucidating the mechanism of drug resistance, but also lays a new foundation for the drug delivery system of breast cancer treatment.

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History
  • Received:December 28,2018
  • Revised:February 15,2019
  • Adopted:February 18,2019
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