ArticleOncotarget2016
Matrix stiffness-mediated effects on stemness characteristics occurring in HCC cells.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 68 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
68 citing papers in PubMed, 124 citations in OpenAlex.
- Extracellular matrix stiffness in hepatocellular carcinoma: mechanisms and targeted therapeutic strategies.Frontiers in immunology · 2026Review
- Exploring Matrix Stiffness-Related Gene in Periodontitis: A Comprehensive Multidataset Analysis.Mediators of inflammation · 2026Article
- Review
- Tissue mechanics in tumor heterogeneity and aggression.Trends in cancer · 2025Review
- Systemic Therapy for Unresectable Hepatocellular Carcinoma: Current Landscape and Future Directions.International journal of molecular sciences · 2025Review
- Review
- WTAP-mediated N6-methyladenine Modification of circEEF2 Promotes Lung Adenocarcinoma Tumorigenesis by Stabilizing CANT1 in an IGF2BP2-dependent Manner.Molecular biotechnology · 2025Article
- Patient-Derived Colorectal Cancer Extracellular Matrices Modulate Cancer Cell Stemness Markers.International journal of molecular sciences · 2025Article
- The first embryo, the origin of cancer and animal phylogeny. V. Cancer stem cells as the unifying biomechanical principle between embryology and oncology.Mechanobiology in medicine · 2025Review
- A glucose-enriched lung pre-metastatic niche triggered by matrix stiffness-tuned exosomal miRNAs in hepatocellular carcinoma.Nature communications · 2025Article
- Cancer stem cells in hepatocellular carcinoma: therapy resistance and emerging treatments.Frontiers in immunology · 2025Review
- Article
- The influence of biophysical niche on tumor-associated macrophages in liver cancer.Hepatology communications · 2024Review
- Tim-1-mediated extracellular matrix promotes the development of hepatocellular carcinoma.Acta biochimica et biophysica Sinica · 2024Article
- The impact of matrix stiffness on hepatic cell function, liver fibrosis, and hepatocellular carcinoma-Based on quantitative data.Biophysics reviews · 2024Review
- Cancer stem cell-immune cell crosstalk in the tumor microenvironment for liver cancer progression.Frontiers of medicine · 2024Review
- LARP4B promotes hepatocellular carcinoma progression and impairs sorafenib efficacy by activating SPINK1-mediated EGFR pathway.Cell death discovery · 2024Article
- Role and potential therapeutic strategies of matrix mechanics for optimizing tumor radiotherapy.Mechanobiology in medicine · 2024Review
- Extracellular Matrix Cues Regulate Mechanosensing and Mechanotransduction of Cancer Cells.Cells · 2024Review
- Functional Roles of CD133: More than Stemness Associated Factor Regulated by the Microenvironment.Stem cell reviews and reports · 2024Review
8 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
14 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Matrix stiffness as an important physical attribute of extracellular matrix exerts significant impacts on biological behaviors of cancer cells such as growth, proliferation, motility, metabolism and invasion. However, its influence on cancer stemness still remains elusive. Here, we explore whether matrix stiffness-mediated effects on stemness characteristics occur in HCC cells. As the substrate stiffness increased, HCC cells exhibited high proportion of cells with CD133(+)/EpCAM(+), high expression levels of CD133, EpCAM, Nanog and SOX2, greater self-renewing ability and oxaliplatin resistance. Simultaneously, their phosphorylation levels of Akt and mTOR, as well as p-4E-BP and SOX2 expressions were also obviously upregulated. Conversely, knockdown of integrin β1 partially attenuated higher stiffness-mediated stemness characteristics in HCC cells, and reversed the phosphorylation levels of Akt and mTOR, and expressions of p-4E-BP and SOX2, suggesting that integrin β1 may deliver higher stiffness signal into HCC cells and activate mTOR signaling pathway. Additionally, mTOR inhibitor suppressed the mTOR phosphorylation level and expression levels of p-4E-BP and SOX2 in HCC cells grown on higher stiffness substrate, as well as depressed their stemness properties significantly, favoring a regulating role of mTOR signaling pathway in matrix stiffness-mediated effects on stemness. In summary, matrix stiffness may be involved in the process of stemness regulation via activating integrin β1/Akt/mTOR/SOX2 signaling pathway. To the best of our knowledge, this study first reveals a novel regulating pathway to direct the stemness characteristics in HCC cells.
Indexed as
Identifiers
What OpenQuestion holds
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.