Proteomic\nand Phosphoproteomic Profiling of Matrix\nStiffness-Induced Stemness-Dormancy State Transition in Breast Cancer\nCells

The dormancy of cancer stem cells is a major factor leading\nto\ndrug resistance and a high rate of late recurrence and mortality in\nestrogen receptor-positive (ER+) breast cancer. Previously, we demonstrated\nthat a stiffer matrix induces tumor cell dormancy and drug resistance,\nwhereas a softened matrix promotes tumor cells to exhibit a stem cell\nstate with high proliferation and migration. In this study, we present\na comprehensive analysis of the proteome and phosphoproteome in response\nto gradient changes in matrix stiffness, elucidating the mechanisms\nbehind cell dormancy-induced drug resistance. Overall, we found that\nantiapoptotic and membrane transport processes may be involved in\nthe mechanical force-induced dormancy resistance of ER+ breast cancer\ncells. Our research provides new insights from a holistic proteomic\nand phosphoproteomic perspective, underscoring the significant role\nof mechanical forces stemming from the stiffness of the surrounding\nextracellular matrix as a critical regulatory factor in the tumor\nmicroenvironment.