ArticleCancer research2016
Tissue Stiffness and Hypoxia Modulate the Integrin-Linked Kinase ILK to Control Breast Cancer Stem-like Cells.
Article in Cancer research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 96 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
96 citing papers in PubMed, 133 citations in OpenAlex.
- Plasma proteome-metabolome signatures enable non-invasive early detection and lymph node risk stratification in breast cancer.Molecular cancer · 2026Article
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- Stiffness-related stress granules promote the metastasis of early-stage oral squamous cell carcinoma via anoikis resistance.Cellular oncology (Dordrecht, Netherlands) · 2026Article
- Unlocking the Therapeutic Potential of Integrin-Linked Kinase Inhibitors in Bioengineered 3D Breast Tumor Stroma Models.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- Comprehensive investigation of the molecular basis of cancer dependencies suggests therapeutic options for breast cancer.Cancer biology & medicine · 2025Article
- Review
- Interfacial Stress Regulates Plasticity and Drug Resistance at the Breast Cancer-Host Interface.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Substrate stiffness regulates triple-negative breast cancer signaling through CXCR4 receptor dynamics.Scientific reports · 2025Article
- Tissue mechanics in tumor heterogeneity and aggression.Trends in cancer · 2025Review
- Article
- Patient-Derived Colorectal Cancer Extracellular Matrices Modulate Cancer Cell Stemness Markers.International journal of molecular sciences · 2025Article
- Forcing the code: tension modulates signaling to drive morphogenesis and malignancy.Genes & development · 2025Review
- Unveiling the potential of biomechanics in pioneering innovative strategies for cancer therapy.Theranostics · 2025Review
- Insights into the mechanisms, regulation, and therapeutic implications of extracellular matrix stiffness in cancer.Bioengineering & translational medicine · 2025Review
- The Hippo Pathway in Breast Cancer: The Extracellular Matrix and Hypoxia.International journal of molecular sciences · 2024Review
- Myofibroblasts derived type V collagen promoting tissue mechanical stress and facilitating metastasis and therapy resistance of lung adenocarcinoma cells.Cell death & disease · 2024Article
- The impact of tumor microenvironment: unraveling the role of physical cues in breast cancer progression.Cancer metastasis reviews · 2024Review
- Stiffened tumor microenvironment enhances perineural invasion in breast cancer via integrin signaling.Cellular oncology (Dordrecht, Netherlands) · 2024Article
- Role and potential therapeutic strategies of matrix mechanics for optimizing tumor radiotherapy.Mechanobiology in medicine · 2024Review
- Tumor Microenvironment: A Niche for Cancer Stem Cell Immunotherapy.Stem cell reviews and reports · 2024Review
36 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Breast tumors are stiffer and more hypoxic than nonmalignant breast tissue. Here we report that stiff and hypoxic microenvironments promote the development of breast cancer stem-like cells (CSC) through modulation of the integrin-linked kinase ILK. Depleting ILK blocked stiffness and hypoxia-dependent acquisition of CSC marker expression and behavior, whereas ectopic expression of ILK stimulated CSC development under softer or normoxic conditions. Stiff microenvironments also promoted tumor formation and metastasis in ovo, where depleting ILK significantly abrogated the tumorigenic and metastatic potential of invasive breast cancer cells. We further found that the ILK-mediated phenotypes induced by stiff and hypoxic microenvironments are regulated by PI3K/Akt. Analysis of human breast cancer specimens revealed an association between substratum stiffness, ILK, and CSC markers, insofar as ILK and CD44 were expressed in cancer cells located in tumor regions predicted to be stiff. Our results define ILK as a key mechanotransducer in modulating breast CSC development in response to tissue mechanics and oxygen tension. Cancer Res; 76(18); 5277-87. ©2016 AACR.
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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.