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

被引：74

作者：

Qin, Xiang ^{[1
,3
]}

Lv, Xiaoying ^{[1
]}

Li, Ping ^{[1
]}

Yang, Rui ^{[1
]}

Xia, Qiong ^{[1
]}

Chen, Yu ^{[1
]}

Peng, Yueting ^{[1
]}

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, Chuan ^{[2
]}

Zhu, Jie ^{[2
]}

You, Fengming ^{[2
]}

Wang, Heng ^{[4
]}

Chen, Jiong ^{[4
]}

Liu, Yiyao ^{[1
,2
]}

机构：

[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

来源：

BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE | 2020年 / 1866卷 / 03期

基金：

中国国家自然科学基金; 中国博士后科学基金;

关键词：

Matrix stiffness; ILK; YAP; Drug resistance; Mechanotransduction; INTEGRIN-LINKED KINASE; EXTRACELLULAR-MATRIX; IN-VITRO; RIGIDITY; EXPRESSION;

D O I：

10.1016/j.bbadis.2019.165625

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

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.

引用

页数：10

共 43 条

[1]

Bahk YW, 2010, NUCL MED MOLEC IMAG, V44, P1, DOI 10.1007/s13139-009-0003-6

[2] Osimertinib (AZD9291) Enhanced the Efficacy of Chemotherapeutic Agents in ABCB1-and ABCG2-Overexpressing Cells In Vitro, In Vivo, and Ex Vivo [J].