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Proteomic and Phosphoproteomic Analysis Reveals the Mechanisms of High Matrix Stiffness Induced Dormancy and Drug Resistance in Breast Cancer Repopulation Cells

ABSTRACT: Cell dormancy is a major factor leading to drug resistance as well as the high rate of late recurrence and mortality in estrogen receptor-positive (ER+) breast cancer. Although some studies have highlighted the significant impact of the microenvironment on dormant cells, they have largely overlooked the mechanical forces stemming from the stiffness of the surrounding extracellular matrix. Previously, we demonstrated that soft matrix promotes tumor cell proliferation and migration, while stiff matrix induces tumor cell dormancy and drug resistance. 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 membrane transport and anti-apoptotic processes may be mainly involved in mechanical force induced dormancy resistance of ER+ breast cancer cells.

ORGANISM(S): Homo Sapiens

SUBMITTER: Juntao Yang

PROVIDER: PXD046799 | iProX | Wed Sep 11 00:00:00 BST 2024

REPOSITORIES: iProX

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