Matrix stiffness modulates ILK-mediated YAP activation to control the drug resistance of breast cancer cells

BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE

卷:1866

Article

Qin, Xiang^1,3  Lv, Xiaoying¹  Li, Ping¹  Yang, Rui¹  Xia, Qiong¹  Chen, Yu¹  Peng, Yueting¹  Li, Li^1,3  Li, Shun^1,3  Li, Tingting^1,3  Jiang, Ying^1,3  Yang, Hong^1,3  Wu, Chunhui^1,3  Zheng, Chuan²  Zhu, Jie²  You, Fengming²  Wang, Heng⁴  Chen, Jiong⁴  Liu, Yiyao^1,2 

[1] Univ Elect Sci & Technol China, Sch Life Sci & Technol, Dept Biophys, Chengdu 610054, Sichuan, Peoples R China

[2] Hosp Chengdu Univ Tradit Chinese Med, 39 Shi Er Qiao Rd, Chengdu 610072, Sichuan, Peoples R China

[3] Univ Elect Sci & Technol China, Ctr Informat Biol, Chengdu 610054, Sichuan, Peoples R China

[4] Nanjing Univ, MOE Key Lab Model Anim Dis Study, State Key Lab Pharmaceut Biotechnol, Model Anim Res Ctr, Nanjing 210061, Jiangsu, Peoples R China

关键词: Matrix stiffness;    ILK;    YAP;    Drug resistance;    Mechanotransduction;   

DOI  :  10.1016/j.bbadis.2019.165625

来源: Elsevier

【 摘 要 】

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.

【 授权许可】

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