ArticleMolecular biology of the cell2015
Microenvironment rigidity modulates responses to the HER2 receptor tyrosine kinase inhibitor lapatinib via YAP and TAZ transcription factors.
Article in Molecular biology of the cell, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 106 papers.
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Who cites it
106 citing papers in PubMed, 154 citations in OpenAlex.
- Hippo pathway at the crossroads of stemness and therapeutic resistance in breast cancer.Molecular oncology · 2026Review
- The Regulation and Function of Hippo/YAP Pathway in Cancer.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Review
- Tumor-Intrinsic PD-1 Regulatory Network Drives Lapatinib Resistance in HER2⁺ Breast Cancer: An Integrative Bioinformatics Analysis.Asian Pacific journal of cancer prevention : APJCP · 2026Article
- Emerin acts as a mechanosensor linking force transmission and disease.Frontiers in oncology · 2026Review
- Drug resistance in cancer: molecular mechanisms and emerging treatment strategies.Molecular biomedicine · 2025Review
- Targeting TAZ-TEAD in minimal residual disease enhances the duration of targeted therapy in melanoma models.Nature communications · 2025Article
- NCAPH-YAP1 interaction promotes breast cancer stemness and tumor progression.Stem cell research & therapy · 2025Article
- Interfacial Stress Regulates Plasticity and Drug Resistance at the Breast Cancer-Host Interface.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- An Agrin-YAP/TAZ Rigidity Sensing Module Drives EGFR-Addicted Lung Tumorigenesis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- NUF2 and NEK2 promote malignant progression of gallbladder cancer by remodeling the extracellular matrix.Carcinogenesis · 2025Article
- It's all downstream from here: RTK/Raf/MEK/ERK pathway resistance mechanisms in glioblastoma.Journal of neuro-oncology · 2025Review
- Stiff extracellular matrix activates the transcription factor ATF5 to promote the proliferation of cancer cells.iScience · 2025Article
- [Research Advances in Targeting the YAP/TAZ Signaling Pathway to Improve Cancer Immunotherapy].Zhongguo fei ai za zhi = Chinese journal of lung cancer · 2025Review
- Design and characterization of an optical phantom for mesoscopic multimodal fluorescence lifetime imaging and optical coherence elastography.Biomedical optics express · 2025Article
- Tumor Cell Spatial Organization Directs EGFR/RAS/RAF Pathway Primary Therapy Resistance through YAP Signaling.bioRxiv : the preprint server for biology · 2025Article
- Forcing the code: tension modulates signaling to drive morphogenesis and malignancy.Genes & development · 2025Review
- HER2-Positive Breast Cancer Treatment and Resistance.Advances in experimental medicine and biology · 2025Review
- GTF2H5 Identified as a crucial synthetic lethal target to counteract chemoresistance in colorectal cancer.Translational oncology · 2024Article
- Extracellular matrix regulation of cell spheroid invasion in a 3D bioprinted solid tumor-on-a-chip.Acta biomaterialia · 2024Article
- Effect of Hydrogel Stiffness on Chemoresistance of Breast Cancer Cells in 3D Culture.Gels (Basel, Switzerland) · 2024Article
46 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
Stiffness is a biophysical property of the extracellular matrix that modulates cellular functions, including proliferation, invasion, and differentiation, and it also may affect therapeutic responses. Therapeutic durability in cancer treatments remains a problem for both chemotherapies and pathway-targeted drugs, but the reasons for this are not well understood. Tumor progression is accompanied by changes in the biophysical properties of the tissue, and we asked whether matrix rigidity modulated the sensitive versus resistant states in HER2-amplified breast cancer cell responses to the HER2-targeted kinase inhibitor lapatinib. The antiproliferative effect of lapatinib was inversely proportional to the elastic modulus of the adhesive substrata. Down-regulation of the mechanosensitive transcription coactivators YAP and TAZ, either by siRNA or with the small-molecule YAP/TEAD inhibitor verteporfin, eliminated modulus-dependent lapatinib resistance. Reduction of YAP in vivo in mice also slowed the growth of implanted HER2-amplified tumors, showing a trend of increasing sensitivity to lapatinib as YAP decreased. Thus we address the role of stiffness in resistance to and efficacy of a HER2 pathway-targeted therapeutic via the mechanotransduction arm of the Hippo pathway.
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Registered trials
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.