ArticleBioMed research international2017
Substrate Stiffness Influences Doxorubicin-Induced p53 Activation via ROCK2 Expression.
Article in BioMed research international, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 34 citations in OpenAlex.
- Myosin-actin pattern links matrix stiffness to GFAT2-hyaluronan metabolism.Materials today. Bio · 2025Article
- p53 at the Crossroads between Doxorubicin-Induced Cardiotoxicity and Resistance: A Nutritional Balancing Act.Nutrients · 2023Review
- Understanding The Regulatory Role of USP32 and SHMT2 in The Progression of Gastric Cancer.Cell journal · 2023Article
- Actin crosslinking by α-actinin averts viscous dissipation of myosin force transmission in stress fibers.iScience · 2023Article
- Article
- 5-Aminolevulinic Acid-Mediated Photodynamic Therapy Potentiates the Effectiveness of Doxorubicin in Ewing Sarcomas.Biomedicines · 2022Article
- Matrix stiffness exacerbates the proinflammatory responses of vascular smooth muscle cell through the DDR1-DNMT1 mechanotransduction axis.Bioactive materials · 2022Article
- Fibrous stroma: Driver and passenger in cancer development.Science signaling · 2022Review
- Article
- Matrix Stiffness Contributes to Cancer Progression by Regulating Transcription Factors.Cancers · 2022Review
- Spatiotemporal control of myofibroblast activation in acoustically-responsive scaffolds via ultrasound-induced matrix stiffening.Acta biomaterialia · 2022Article
- circCUL2 regulates gastric cancer malignant transformation and cisplatin resistance by modulating autophagy activation via miR-142-3p/ROCK2.Molecular cancer · 2020Article
- MMP24 as a Target of YAP is a Potential Prognostic Factor in Cancer Patients.Bioengineering (Basel, Switzerland) · 2020Article
- Doxorubicin Promotes Migration and Invasion of Breast Cancer Cells through the Upregulation of the RhoA/MLC Pathway.Journal of breast cancer · 2019Article
- Tumor microenvironment-driven non-cell-autonomous resistance to antineoplastic treatment.Molecular cancer · 2019Review
- Profilin-1 deficiency leads to SMAD3 upregulation and impaired 3D outgrowth of breast cancer cells.British journal of cancer · 2018Article
- Substrate rigidity-dependent positive feedback regulation between YAP and ROCK2.Cell adhesion & migration · 2018Article
- Dynamic interplay between tumour, stroma and immune system can drive or prevent tumour progression.Convergent science physical oncology · 2017Article
Corrections and comments
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Authors and funding
11 authors at 6 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The physical properties of the extracellular matrix (ECM), such as stiffness, are involved in the determination of the characteristics of cancer cells, including chemotherapy sensitivity. Resistance to chemotherapy is often linked to dysfunction of tumor suppressor p53; however, it remains elusive whether the ECM microenvironment interferes with p53 activation in cancer cells. Here, we show that, in MCF-7 breast cancer cells, extracellular stiffness influences p53 activation induced by the antitumor drug doxorubicin. Cell growth inhibition by doxorubicin was increased in response to ECM rigidity in a p53-dependent manner. The expression of Rho-associated coiled coil-containing protein kinase (ROCK) 2, which induces the activation of myosin II, was significantly higher when cells were cultured on stiffer ECM substrates. Knockdown of ROCK2 expression or pharmacological inhibition of ROCK decreased doxorubicin-induced p53 activation. Our results suggest that a soft ECM causes downregulation of ROCK2 expression, which drives resistance to chemotherapy by repressing p53 activation.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.