Heterogeneous Responses to Mechanical Force of Prostate Cancer Cells Inducing Different Metastasis Patterns

Abstract The physical cues in the extracellular environment play important roles in cancer cell metastasis. However, how metastatic cancer cells respond to the diverse mechanical environments of metastatic sites is not fully understood. Here, substrates with different mechanical properties are prepared to simulate the extracellular mechanical environment of various human tissues. The prostate cancer (PC) cells derived from different cancer metastasis sites show heterogeneity in mechanical response. This heterogeneity mediates two distinct metastasis patterns. High stiffness promotes individual cell migration and proliferation by inducing Yes‐associated protein and tafazzin (YAP/TAZ) nuclear localization in bone metastasis‐derived cells, whereas low stiffness promotes cell migration and proliferation by inducing lymphatic metastasis‐derived cells to form clusters characterized by high expression of CD44. The different metastasis patterns induced by the mechanical properties of the extracellular environment are crucial in the development of PC.