The migration of metastatic breast cancer cells is regulated by matrix stiffness via YAP signalling

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.

PDMS stiffness was measured by microindentation using a Biomomentum Mach-1 system (Biomomentum Inc) as described previously (Ireland et al., 2020).

Keywords: Cell mobility; Matrix stiffness; Mechanosensing; Metastatic breast cancer; YAP