ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2021
Chemotherapy-Enriched THBS2-Deficient Cancer Stem Cells Drive Hepatocarcinogenesis through Matrix Softness Induced Histone H3 Modifications.
Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 48 citations in OpenAlex.
- Immune-epigenetic convergence in biomaterial-guided tissue regeneration.Materials today. Bio · 2026Article
- Neuroprotective Role of THBS2 in Experimental Spinal Cord Injury Via its Anti-neuroinflammatory and Anti-apoptotic Properties.Biochemical genetics · 2026Article
- THBS2 as a Key Regulator in Gastrointestinal Tumors: from Molecular Mechanisms to Clinical Applications.Current oncology reports · 2026Review
- Cancer cells metastasize in several types of cancer via two distinct routes, probably based on mechanical signals.Frontiers in cell and developmental biology · 2026Review
- Extracellular matrix stiffness in hepatocellular carcinoma: mechanisms and targeted therapeutic strategies.Frontiers in immunology · 2026Review
- The Role of Extracellular Proteases and Extracellular Matrix Remodeling in the Pre-Metastatic Niche.Biomolecules · 2025Review
- Tumor peripheral stiffness modulates lenvatinib resistance in HCC preclinical models by regulating FIS1-dependent mitophagy.JHEP reports : innovation in hepatology · 2025Article
- NONO links circadian rhythm disruption and enhanced tumor-fibroblast crosstalk in right-sided colorectal cancer.Biomarker research · 2025Article
- Cancer stem cells: Bridging microenvironmental interactions and clinical therapy.Clinical and translational medicine · 2025Review
- Local soft niches in mechanically heterogeneous primary tumors promote brain metastasis via mechanotransduction-mediated HDAC3 activity.Science advances · 2025Article
- Cancer stem cells in hepatocellular carcinoma: therapy resistance and emerging treatments.Frontiers in immunology · 2025Review
- The role of liver cancer stem cells in hepatocellular carcinoma metastasis.Cancer biology & therapy · 2024Review
- The impact of matrix stiffness on hepatic cell function, liver fibrosis, and hepatocellular carcinoma-Based on quantitative data.Biophysics reviews · 2024Review
- Phenotypic Heterogeneity, Bidirectionality, Universal Cues, Plasticity, Mechanics, and the Tumor Microenvironment Drive Cancer Metastasis.Biomolecules · 2024Review
- Role and therapeutic potential of E3s in the tumor microenvironment of hepatocellular carcinoma.Frontiers in immunology · 2024Review
- Functional Roles of CD133: More than Stemness Associated Factor Regulated by the Microenvironment.Stem cell reviews and reports · 2024Review
- Cancer-associated fibroblasts and prostate cancer stem cells: crosstalk mechanisms and implications for disease progression.Frontiers in cell and developmental biology · 2024Review
- SPINK1-induced tumor plasticity provides a therapeutic window for chemotherapy in hepatocellular carcinoma.Nature communications · 2023Article
- Targeting the mechano-microenvironment and liver cancer stem cells: a promising therapeutic strategy for liver cancer.Cancer biology & medicine · 2023Review
- Biophysics in tumor growth and progression: from single mechano-sensitive molecules to mechanomedicine.Oncogene · 2023Review
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Authors and funding
12 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The physical microenvironment is a critical mediator of tumor behavior. However, detailed biological and mechanistic insight is lacking. The present study reveals the role of chemotherapy-enriched CD133+ liver cancer stem cells (CSCs) with THBS2 deficiency. This subpopulation of cells contributes to a more aggressive cancer and functional stemness phenotype in hepatocellular carcinoma (HCC) by remodeling the extracellular matrix (ECM) through the regulation of matrix metalloproteinase (MMP) activity, collagen degradation, and matrix stiffness. The local soft spots created by these liver CSCs can enhance stemness and drug resistance and provide a route of escape to facilitate HCC metastasis. Interestingly, a positive feed-forward loop is identified where a local soft spot microenvironment in the HCC tumor is enriched with CD133 expressing cells that secrete markedly less ECM-modifying THBS2 upon histone H3 modification at its promoter region, allowing the maintenance of a localized soft spot matrix. Clinically, THBS2 deficiency is also correlated with low HCC survival, where high levels of CSCs with low THBS2 expression in HCC are associated with decreased collagen fiber deposits and an invasive tumor front. The findings have implications for the treatment of cancer stemness and for the prevention of tumor outgrowth through disseminated tumor cells.
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