Proteomic and Phosphoproteomic Profiling of Matrix Stiffness-Induced Stemness-Dormancy State Transition in Breast Cancer Cells

The dormancy of cancer stem cells is a major factor leading
to
drug resistance and a high rate of late recurrence and mortality in
estrogen receptor-positive (ER+) breast cancer. Previously, we demonstrated
that a stiffer matrix induces tumor cell dormancy and drug resistance,
whereas a softened matrix promotes tumor cells to exhibit a stem cell
state with high proliferation and migration. In this study, we present
a comprehensive analysis of the proteome and phosphoproteome in response
to gradient changes in matrix stiffness, elucidating the mechanisms
behind cell dormancy-induced drug resistance. Overall, we found that
antiapoptotic and membrane transport processes may be involved in
the mechanical force-induced dormancy resistance of ER+ breast cancer
cells. Our research provides new insights from a holistic proteomic
and phosphoproteomic perspective, underscoring the significant role
of mechanical forces stemming from the stiffness of the surrounding
extracellular matrix as a critical regulatory factor in the tumor
microenvironment.