ArticleMechanobiology in medicine2023
Extracellular cell matrix stiffness-driven drug resistance of breast cancer cells via EGFR activation.
Article in Mechanobiology in medicine, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed.
- Spatially organized regulated cell death-immune coupling in solid tumors: integrating spatial omics with actionable regulated cell death biology.Molecular cancer · 2026Review
- Mechanobiology of the tumor microenvironment: a review of therapeutic interactions and in vitro elasticity measurement techniques.Journal of biomedical science · 2026Review
- Mechanical forces of beating heart suppress cancer growth.Mechanobiology in medicine · 2026Article
- Smart hydrogels for overcoming cancer multidrug resistance.Molecular cancer · 2026Review
- Photocrosslinkable lung dECM hydrogels promote stiffness-dependent lung cancer growth and chemoresistance.Materials today. Bio · 2026Article
- Beyond the membrane: rethinking EGFR signaling in physiology and cancer.Cellular and molecular life sciences : CMLS · 2026Review
- Mechanical memory in cells: mechanisms, effects, and applications in regenerative medicine.Frontiers in bioengineering and biotechnology · 2026Review
- Drug resistant glioblastoma stem cells exhibit enriched stemness signatures and share extracellular matrix overexpression.BMC cancer · 2025Article
- Review
- Mapping thirty years of tumour-microenvironment-driven drug resistance in breast cancer: a global bibliometric analysis.Discover oncology · 2025Article
- Deciphering Mitochondria: Unveiling Their Roles in Mechanosensing and Mechanotransduction.Research (Washington, D.C.) · 2025Review
- Biochemical hallmarks-targeting antineoplastic nanotherapeutics.Bioactive materials · 2024Review
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10 authors.
Funding
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Abstract
Tumor progression is accompanied by complex structural changes in the extracellular matrix (ECM), which decrease the effective exposure of tumors to drugs. Breast cancer are highly heterogeneous with a typically high degree of ECM remodeling and stiffening. Therefore, it is especially important to explore the influence of ECM stiffness on breast cancer chemotherapy. Here, we fabricated 3D Methacrylate Gelatin (GelMA) hydrogels with varying stiffness by photo-crosslinking to simulate the change of tissue stiffness during the development of breast cancer. These 3D hydrogels were used to evaluate how MDA-MB-231 cells responded to the chemotherapy drug doxorubicin (DOX), the mechanical regulatory mechanism involved has also been investigated. The findings demonstrated that 15% GelMA hydrogel (9 kPa) increased the activity of EGFR to block the Hippo signaling pathway and activate Yes-associated protein (YAP). Activated YAP allowed cytosolic EGFR transport into the nucleus via binding with it, up-regulated the expression of their respective transcriptional targets, and thus generates drug resistance. Altogether, our study implicates that stiffness-dependent EGFR activation plays an important role in breast cancer drug resistance, indicating that targeting of both YAP and EGFR signals may present a promising therapeutic strategy for ECM stiffness-induced drug resistance.
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