The migration of metastatic breast cancer cells is regulated by matrix stiffness via YAP signalling
Wei Chen,
Shihyun Park,
Chrishma Patel,
Yuxin Bai,
Karim Henary,
Arjun Raha,
Saeed Mohammadi,
Lidan You,
Fei Geng
Affiliations
Wei Chen
Department of Mechanical Engineering, McMaster University, Hamilton, ON L8S 0A3, Canada
Shihyun Park
Faculty of Health Sciences, McMaster University, Hamilton, ON L8S 4K1, Canada
Chrishma Patel
Faculty of Health Sciences, McMaster University, Hamilton, ON L8S 4K1, Canada
Yuxin Bai
Faculty of Health Sciences, McMaster University, Hamilton, ON L8S 4K1, Canada
Karim Henary
Department of Mechanical Engineering, McMaster University, Hamilton, ON L8S 0A3, Canada
Arjun Raha
Department of Mechanical Engineering, McMaster University, Hamilton, ON L8S 0A3, Canada
Saeed Mohammadi
W Booth School of Engineering Practice and Technology, McMaster University, Hamilton, ON L8S 0A3, Canada
Lidan You
Department of Mechanical & Industrial Engineering, University of Toronto, Toronto, ON M5S 3G8, Canada
Fei Geng
Department of Mechanical Engineering, McMaster University, Hamilton, ON L8S 0A3, Canada; W Booth School of Engineering Practice and Technology, McMaster University, Hamilton, ON L8S 0A3, Canada; Corresponding author.
Matrix stiffness is a driver of breast cancer progression and mechanosensitive transcriptional activator YAP plays an important role in this process. However, the interplay between breast cancer and matrix stiffness, and the significance of this interplay remained largely unknown. Here, we showed an increase in YAP nuclear localization and a higher proliferation rate in both highly metastatic MDA-MB-231 cells and the non-metastatic counterpart MCF-7 cells when they were exposed to the stiff matrix. However, in response to the stiff matrix highly metastatic MDA-MB-231 cells instead of MCF-7 cells exhibited upregulated mobility, which was shown to be YAP-dependent. Consistently, MDA-MB-231 cells exhibited different focal adhesion dynamics from MCF-7 cells in response to matrix stiffness. These results suggested a YAP-dependent mechanism through which matrix stiffness regulates the migratory potential of metastatic breast cancer cells.
