title: Regulation of matrix stiffness on the epithelial-mesenchymal transition of breast cancer cells under hypoxia environment.
abstract: Substrate stiffness and hypoxia are associated with tumor development and progression, respectively. However, the synergy of them on the biological behavior of human breast cancer cell is still largely unknown. This study explored how substrate stiffness regulates the cell phenotype, viability, and epithelial-mesenchymal transition (EMT) of human breast cancer cells MCF-7 under hypoxia (1% O2). TRITC-phalloidin staining showed that MCF-7 cells transformed from round to irregular polygon with stiffness increase either in normoxia or hypoxia. While being accompanied with the upward tendency from a 0.5- to a 20-kPa substrate, the percentage of cell apoptosis was significantly higher in hypoxia than that in normoxia, especially on the 20-kPa substrate. Additionally, it was hypoxia, but not normoxia, that promoted the EMT of MCF-7 by upregulating hypoxia-inducible factor-1α (HIF-1α), vimentin, Snail 1, and matrix metalloproteinase 2 (MMP 2) and 9 (MMP 9), and downregulating E-cadherin simultaneously regardless of the change of substrate stiffness. In summary, this study discovered that hypoxia and stiffer substrate (20 kPa) could synergistically induce phenotype change, apoptosis, and EMT of MCF-7 cells. Results of this study have an important significance on further exploring the synergistic effect of stiffness and hypoxia on the EMT of breast cancer cells and its molecular mechanism.
authors.affiliation: Key Laboratory of Biorheological Science and Technology, Ministry of Education, Bioengineering College, Chongqing University, Chongqing, 400044, People's Republic of China. yglv@cqu.edu.cn.|Mechanobiology and Regenerative Medicine Laboratory, Bioengineering College, Chongqing University, 174 Shazheng Street, Shapingba District, Chongqing, 400044, People's Republic of China. yglv@cqu.edu.cn.
authors.forename: Yonggang
authors.identifier: http://orcid.org/0000-0003-3966-8975
authors.initials: Y
authors.lastname: Lv
authors.affiliation: Key Laboratory of Biorheological Science and Technology, Ministry of Education, Bioengineering College, Chongqing University, Chongqing, 400044, People's Republic of China.|Mechanobiology and Regenerative Medicine Laboratory, Bioengineering College, Chongqing University, 174 Shazheng Street, Shapingba District, Chongqing, 400044, People's Republic of China.
authors.forename: Can
authors.initials: C
authors.lastname: Chen
authors.affiliation: Key Laboratory of Biorheological Science and Technology, Ministry of Education, Bioengineering College, Chongqing University, Chongqing, 400044, People's Republic of China.|Mechanobiology and Regenerative Medicine Laboratory, Bioengineering College, Chongqing University, 174 Shazheng Street, Shapingba District, Chongqing, 400044, People's Republic of China.
authors.forename: Boyuan
authors.initials: B
authors.lastname: Zhao
authors.affiliation: Key Laboratory of Biorheological Science and Technology, Ministry of Education, Bioengineering College, Chongqing University, Chongqing, 400044, People's Republic of China.|Mechanobiology and Regenerative Medicine Laboratory, Bioengineering College, Chongqing University, 174 Shazheng Street, Shapingba District, Chongqing, 400044, People's Republic of China.
authors.forename: Xiaomei
authors.initials: X
authors.lastname: Zhang
mesh_terms: D017209:Apoptosis; D001943:Breast Neoplasms / Q000235:genetics / Q000503:physiopathology*; D015687:Cell Hypoxia / Q000502:physiology*; D048430:Cell Shape; D058750:Epithelial-Mesenchymal Transition / Q000502:physiology*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D061986:MCF-7 Cells
keywords: Breast cancer cell; Epithelial-mesenchymal transition; Hypoxia; Phenotype; Substrate stiffness