ArticleCancer research2020
Soft Microenvironments Induce Chemoresistance by Increasing Autophagy Downstream of Integrin-Linked Kinase.
Article in Cancer research, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 45 citations in OpenAlex.
- Single-cell transcriptomics identify mechanical-memory-associated cell states in metastatic HRBreast cancer research : BCR · 2026Article
- Cancer stem cell heterogeneity‑inspired therapeutics for enhancing tumor treatment outcomes (Review).International journal of oncology · 2026Review
- Multi-omics investigation reveals molecular determinants of cancer cell evolution on soft extracellular matrix.bioRxiv : the preprint server for biology · 2025Article
- Myosin-actin pattern links matrix stiffness to GFAT2-hyaluronan metabolism.Materials today. Bio · 2025Article
- Breast cancer cell coculture induces normal lung fibroblast transition to CAFs, promoting tumor cell dormancy and therapy resistance.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- An in vitro hydrogel-based model to study dormancy associated drug resistance in metastatic breast cancer spheroids.npj biomedical innovations · 2025Article
- Syntaxin-6 mediated autophagy confers lenvatinib resistance in hepatocellular carcinoma.Oncogene · 2025Article
- Review
- Soft matrix promotes immunosuppression in tumor-resident immune cells via COX-FGF2 signaling.Nature communications · 2025Article
- Lung-specific metastasis: the coevolution of tumor cells and lung microenvironment.Molecular cancer · 2025Review
- Extracellular matrix stiffness: mechanisms in tumor progression and therapeutic potential in cancer.Experimental hematology & oncology · 2025Review
- Unveiling Matrix Metalloproteinase 13's Dynamic Role in Breast Cancer: A Link to Physical Changes and Prognostic Modulation.International journal of molecular sciences · 2025Review
- Inhibition of autophagy in platelets as a therapeutic strategy preventing hypoxia induced thrombosis.Scientific reports · 2025Article
- Dual role of autophagy in bone metastasis: mechanistic insights and therapeutic targeting.American journal of clinical and experimental urology · 2025Review
- Matrix stiffness boosts PDAC chemoresistance via SCD1-dependent lipid metabolic reprogramming.Regenerative biomaterials · 2025Article
- Premetastatic niche mechanics and organotropism in breast cancer.npj biological physics and mechanics · 2025Review
- Insights into the mechanisms, regulation, and therapeutic implications of extracellular matrix stiffness in cancer.Bioengineering & translational medicine · 2025Review
- Stromal softness confines pancreatic cancer growth through lysosomal-cathepsin mediated YAP1 degradation.Cellular and molecular life sciences : CMLS · 2024Article
- Review
- Exploiting Matrix Stiffness to Overcome Drug Resistance.ACS biomaterials science & engineering · 2024Review
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Breast cancer relapse can develop over the course of years as a result of dormant cancer cells that disseminate to secondary sites. These dormant cells are often resistant to conventional hormone and chemotherapy. Although recurrence is the main cause of death from cancer, microenvironmental factors that may influence resistance to therapy and duration of dormancy are largely unknown. Breast cancer relapse is often detected in tissues that are softer than the normal mammary gland or the primary breast tumor, such as bone marrow, brain, and lung. We therefore explored how stiffness of the microenvironment at secondary sites regulates tumor dormancy and the response of breast cancer cells to hormone and chemotherapy. In soft microenvironments reminiscent of metastatic sites, breast cancer cells were more resistant to the estrogen receptor modulator tamoxifen as a result of increased autophagy and decreased expression of estrogen receptor-α. Consistently, pharmacologic inhibition or genetic downregulation of autophagy increased the response of breast cancer cells to tamoxifen on soft substrata. In addition, autophagy was decreased downstream of integrin-linked kinase on stiff substrata. Altogether, our data show that tissue mechanics regulates therapeutic outcome and long-term survival of breast cancer cells by influencing autophagy. SIGNIFICANCE: These findings characterize the persistence of dormant cells at metastatic sites, where soft microenvironments downregulate estrogen receptor expression and upregulate autophagy, thereby promoting therapy resistance in breast cancer cells. GRAPHICAL ABSTRACT: http://cancerres.aacrjournals.org/content/canres/80/19/4103/F1.large.jpg.
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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.