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

Rong Han ¹, Xu Sun ¹, Yue Wu ¹

⁰Department of Immunology & State Key Laboratory of Common Mechanism Research for Major Diseases, Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences (CAMS) & Peking Union Medical College, Beijing 10050, China.

Journal of Proteome Research +

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September 19, 2024

View abstract on PubMed

Summary

Tumor matrix stiffness drives dormancy and drug resistance in estrogen receptor-positive breast cancer. Understanding these mechanical forces reveals key anti-apoptotic and transport mechanisms involved in cancer cell survival.

Area Of Science

Biomedical Engineering
Cancer Biology
Proteomics

Background

Cancer stem cell dormancy is a key driver of drug resistance and recurrence in estrogen receptor-positive (ER+) breast cancer.
Extracellular matrix (ECM) stiffness influences tumor cell behavior, with stiffer matrices inducing dormancy and drug resistance, while softer matrices promote proliferation and migration.

Purpose Of The Study

To comprehensively analyze the proteome and phosphoproteome of ER+ breast cancer cells in response to varying matrix stiffness.
To elucidate the molecular mechanisms underlying mechanical force-induced dormancy and drug resistance.

Main Methods

Proteomic and phosphoproteomic analysis of ER+ breast cancer cells cultured on matrices with gradient stiffness.
Bioinformatic analysis to identify key biological processes and signaling pathways affected by matrix stiffness.

Main Results

Significant alterations in protein and phosphoprotein expression were observed in response to changes in ECM stiffness.
Antiapoptotic and membrane transport processes were identified as potentially involved in mechanical force-induced dormancy and drug resistance.

Conclusions

Matrix stiffness is a critical regulator of the tumor microenvironment, influencing ER+ breast cancer cell dormancy and drug resistance.
Proteomic and phosphoproteomic analyses provide novel insights into the mechanisms by which mechanical forces contribute to therapeutic resistance.

Keywords:

breast cancer cancer dormancy cancer stem cell drug resistance mechanical force