ArticleMolecular cancer2024
THBS2 + cancer-associated fibroblasts promote EMT leading to oxaliplatin resistance via COL8A1-mediated PI3K/AKT activation in colorectal cancer.
Article in Molecular cancer, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 68 papers, 1 of them a synthesis that pooled it.
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Who cites it
68 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Type VIII collagen: advances in matrix biology and translational promise.Frontiers in bioengineering and biotechnology · 2025Pooled it
- Colitis-Associated Colorectal Cancer-STAT3 Inhibition as a Preventive Strategy.International journal of molecular sciences · 2026Article
- SDC1Gut · 2026Article
- Mechanisms and advances of drug resistance in colorectal cancer: A systematic overview of multi-layered regulatory networks.Translational oncology · 2026Review
- ReducedTranslational andrology and urology · 2026Article
- PI3K/AKT signaling pathway: molecular crossroads in tumorigenesis and therapeutic innovation.Signal transduction and targeted therapy · 2026Review
- Epithelial-mesenchymal transition in carcinoma: navigating phenotypic states to target resistance and metastasis.Cancer metastasis reviews · 2026Review
- Role of epithelial-mesenchymal transition (EMT) in malignancies: current status and future prospects.Signal transduction and targeted therapy · 2026Review
- Cancer drug response and resistance: molecular mechanisms and combating strategies.Signal transduction and targeted therapy · 2026Review
- Myofibroblastic CAF and Malignant Ductal Cell Crosstalk Drives Epithelial-Mesenchymal Transition and Progression in Pancreatic Ductal Adenocarcinoma via THBS2-SDC/Integrin Axes.International journal of molecular sciences · 2026Article
- Longitudinal single-cell and TCR repertoire profiling characterizes clonal entrapment in patients with pMMR/MSS locally advanced rectal cancer.Cell discovery · 2026Article
- Multidrug resistance in cancer: current understandings and future perspective.Molecular biomedicine · 2026Review
- Single-cell analysis identifies dysregulated cell type-specific gene programs and intercellular crosstalk underlying colorectal cancer.NPJ precision oncology · 2026Article
- Multi-Scale Mapping of Gene Expression from Whole-slide Images for Identifying Phenotype-Associated Subpopulations.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Review
- RHBDL2 drives lipid metabolic reprogramming in osteosarcoma via USP3-mediated deubiquitination of PPT1.Cell death & disease · 2026Article
- Cancer-associated fibroblasts and immune escape-related genes serve as biological markers for the prognosis of colorectal cancer.Hereditas · 2026Article
- Proteomic Profiling of Human Extracellular Vesicles Reveals Diagnostic Biomarkers for Colon Adenocarcinoma.Journal of extracellular vesicles · 2026Article
- Cancer-Associated Fibroblasts Functions as Multifunctional Architects of the Tumor Stroma and Represent Emerging Therapeutic Vulnerabilities.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- COL8A1-positive cancer-associated fibroblasts are drivers of 5-fluorouracil resistance in colorectal cancer.Apoptosis : an international journal on programmed cell death · 2026Article
8 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
20 authors.
Funding
Abstract
Cancer-associated fibroblasts (CAFs) exert multiple tumor-promoting functions and are key contributors to drug resistance. The mechanisms by which specific subsets of CAFs facilitate oxaliplatin resistance in colorectal cancer (CRC) have not been fully explored. This study found that THBS2 is positively associated with CAF activation, epithelial-mesenchymal transition (EMT), and chemoresistance at the pan-cancer level. Together with single-cell RNA sequencing and spatial transcriptomics analyses, we identified THBS2 specifically derived from subsets of CAFs, termed THBS2 + CAFs, which could promote oxaliplatin resistance by interacting with malignant cells via the collagen pathway in CRC. Mechanistically, COL8A1 specifically secreted from THBS2 + CAFs directly interacts with the ITGB1 receptor on resistant malignant cells, activating the PI3K-AKT signaling pathway and promoting EMT, ultimately leading to oxaliplatin resistance in CRC. Moreover, elevated COL8A1 promotes EMT and contributes to CRC oxaliplatin resistance, which can be mitigated by ITGB1 knockdown or AKT inhibitor. Collectively, these results highlight the crucial role of THBS2 + CAFs in promoting oxaliplatin resistance of CRC by activating EMT and provide a rationale for a novel strategy to overcome oxaliplatin resistance in CRC.
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