ArticleProceedings of the National Academy of Sciences of the United States of America2015
Tissue stiffness regulates serine/arginine-rich protein-mediated splicing of the extra domain B-fibronectin isoform in tumors.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers, 1 of them a synthesis that pooled it.
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
64 citing papers in PubMed, 1 synthesis or guideline pooled it, 101 citations in OpenAlex.
- Pooled it
- Forces that shape the transcriptome: Linking cellular mechanosensing to mRNA splicing.The Journal of biological chemistry · 2026Review
- Epitranscriptomic sculpting: the role of mMedical oncology (Northwood, London, England) · 2025Review
- The bidirectional interplay between RNA processing and mechanotransduction.Cell reports · 2025Review
- Tissue mechanics in tumor heterogeneity and aggression.Trends in cancer · 2025Review
- A systems-based approach to uterine fibroids identifies differential splicing associated with abnormal uterine bleeding.Communications medicine · 2025Article
- Discoidin Domain Receptors in Tumor Biology and Immunology: Progression and Challenge.Biomolecules · 2025Review
- Age-Related Dysregulation of α5β1 and αvβ3 Integrin Activity Alters Contractile Properties of Trabecular Meshwork Cells.Investigative ophthalmology & visual science · 2025Article
- Article
- Mechanosensitive ion channel-related genes in hepatocellular carcinoma: Unraveling prognostic genes and their roles in drug resistance and immune modulation.Liver research (Beijing, China) · 2025Article
- Insights into the mechanisms, regulation, and therapeutic implications of extracellular matrix stiffness in cancer.Bioengineering & translational medicine · 2025Review
- Cancer-associated fibroblasts derived fibronectin extra domain A promotes sorafenib resistance in hepatocellular carcinoma cells by activating SHMT1.Genes & diseases · 2024Article
- Matrix stiffness-dependent regulation of immunomodulatory genes in human MSCs is associated with the lncRNA CYTOR.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Function of serine/arginine-rich splicing factors in hematopoiesis and hematopoietic malignancies.Cancer cell international · 2024Review
- Unveiling the Role of Mechanical Microenvironment in Hepatocellular Carcinoma: Molecular Mechanisms and Implications for Therapeutic Strategies.International journal of biological sciences · 2024Review
- Targeting extracellular matrix stiffness for cancer therapy.Frontiers in immunology · 2024Review
- Role of elastic fiber degradation in disease pathogenesis.Biochimica et biophysica acta. Molecular basis of disease · 2023Review
- Matrix stiffness regulates tumor cell intravasation through expression and ESRP1-mediated alternative splicing of MENA.Cell reports · 2023Article
- RNA splicing dysregulation and the hallmarks of cancer.Nature reviews. Cancer · 2023Review
- A cuproptosis-related signature for predicting the prognosis of gastric cancer.Journal of gastrointestinal oncology · 2023Article
4 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
8 authors at 1 institution in 1 country.
Funding
Abstract
Alternative splicing of proteins gives rise to different isoforms that play a crucial role in regulating several cellular processes. Notably, splicing profiles are altered in several cancer types, and these profiles are believed to be involved in driving the oncogenic process. Although the importance of alternative splicing alterations occurring during cancer is increasingly appreciated, the underlying regulatory mechanisms remain poorly understood. In this study, we use both biochemical and physical tools coupled with engineered models, patient samples, and a murine model to investigate the role of the mechanical properties of the tumor microenvironment in regulating the production of the extra domain-B (EDB) splice variant of fibronectin (FN), a hallmark of tumor angiogenesis. Specifically, we show that the amount of EDB-FN produced by endothelial cells increases with matrix stiffness both in vitro and within mouse mammary tumors. Matrix stiffness regulates splicing through the activation of serine/arginine rich (SR) proteins, the splicing factors involved in the production of FN isoforms. Activation of the SR proteins by matrix stiffness and the subsequent production of EDB-FN are dependent on intracellular contractility and PI3K-AKT signaling. Notably, matrix stiffness-mediated splicing is not limited to EDB-FN, but also affects splicing in the production of PKC βII and the VEGF 165b splice variant. Together, these results demonstrate that the mechanical properties of the microenvironment regulate alternative splicing and establish a previously unidentified mechanism by which cells can adapt to their microenvironment.
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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.