期刊
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
卷 1866, 期 3, 页码 -出版社
ELSEVIER
DOI: 10.1016/j.bbadis.2019.165625
关键词
Matrix stiffness; ILK; YAP; Drug resistance; Mechanotransduction
资金
- National Natural Science Foundation of China [11772088, 31700811, 11802056, 31800780, 11972111, 31900940, 81671821]
- China Postdoctoral Science Foundation [2018M640904, 2019T120831]
- Basic Research Programs of Sichuan Province Science and Technology Foundation [2017JY0019, 2017JY0217, 2019YJ0183, 2019YJ0184]
- Fundamental Research Funds for the Central Universities [ZYGX2019J117]
One of the hallmarks of cancer progression is strong drug resistance during clinical treatments. The tumor microenvironment is closely associated with multidrug resistance, the optimization of tumor microenvironments may have a strong therapeutic effect. In this study, we configured polyacrylamide hydrogels of varying stiffness [low (10 kPa), intermediate (38 kPa) and high (57 kPa)] to simulate tissue physical matrix stiffness across different stages of breast cancer. After treatment with doxorubicin, cell survival rates on intermediate stiffness substrate are significantly higher. We find that high expression of ILK and YAP reduces the survival rates of breast cancer patients. Drug resistance is closely associated with the inactivation of the hippo pathway protein Merlin/MST/LATS and the activation of YAP. These results not only highlight the understanding of drug resistance mechanisms but also serve as a new basis for developing breast cancer treatment delivery systems.
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