ArticleThe Journal of clinical investigation2022
Targeting FAPα-expressing hepatic stellate cells overcomes resistance to antiangiogenics in colorectal cancer liver metastasis models.
Article in The Journal of clinical investigation, 2022. 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 57 papers, 1 of them a synthesis that pooled it.
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Who cites it
57 citing papers in PubMed, 1 synthesis or guideline pooled it, 73 citations in OpenAlex.
- Advances in bevacizumab in colorectal cancer: a bibliometric analysis from 2004 to 2023.Frontiers in oncology · 2025Pooled it
- Review
- Molecular imaging-guided discovery of a potent natural FAPα inhibitor for liver fibrosis therapy.Nature communications · 2026Article
- Microenvironment-Driven Reprogramming in Colorectal Cancer Liver Metastasis: Metabolic, Phenotypic, and Immune Adaptation.International journal of molecular sciences · 2026Review
- Deciphering Colorectal Liver Metastasis Perfusion Heterogeneity: Identification of Distinct Vascular Phenotypes through High-Lateral-Resolution Photoacoustic Microscopy.Radiology. Imaging cancer · 2026Article
- Targeting FAPActa pharmaceutica Sinica. B · 2026Article
- Prognostic analysis and beneficiary population exploration of subsequent treatment regimens after third-generation EGFR-TKIs failure in EGFR-mutated advanced non-small cell lung cancer: a retrospective cohort study.Translational lung cancer research · 2026Article
- Bispecific antibody engineered extracellular vesicles redirect T cells to prevent postoperative epidural fibrosis.Nature communications · 2026Article
- A magnetic resonance imaging-guided drug delivery system for premetastatic niche theranostics and colorectal cancer liver metastasis intervention.Journal of nanobiotechnology · 2026Article
- S100A6 promotes liver metastasis by activating FGFR3 signaling in BAP1-deficient uveal melanoma.Oncogene · 2026Article
- In Vitro Cell Viability and Migration Inhibitory Effects of Isorhamnetin in Non-Small Cell Lung Cancer Cells.Biomedicines · 2026Article
- Key molecular mechanisms and regulatory networks in colorectal cancer liver metastasis.Biological procedures online · 2026Review
- FAPαAdvanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Paclitaxel drives TREM2Nature communications · 2026Article
- Tumor cell FAP orchestrates EMT and immune suppression in aggressive localized ccRCC.Theranostics · 2026Article
- Validation of fibroblast activation protein and α-smooth muscle actin as prognostic biomarkers in prostate cancer through AI-assisted image analysis of dual-marker IHC.The journal of pathology. Clinical research · 2026Article
- Tumor-Associated Pericytes: Tumorigenicity and Targeting for Cancer Therapy.Current vascular pharmacology · 2026Review
- Myeloid-derived suppressor cells in colorectal cancer: mechanisms of immunosuppression, therapy resistance and therapeutic targeting.Frontiers in cell and developmental biology · 2026Review
- The prognostic value of tumor macroscopic morphology in colorectal cancer.Translational oncology · 2026Article
- Hypoxia-driven tumor immune escape: mechanisms and therapeutic opportunities.Frontiers in immunology · 2026Review
Corrections and comments
- Erratum issued
Authors and funding
25 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Vessel co-option has been demonstrated to mediate colorectal cancer liver metastasis (CRCLM) resistance to antiangiogenic therapy. The current mechanisms underlying vessel co-option have mainly focused on "hijacker" tumor cells, whereas the function of the "hijackee" sinusoidal blood vessels has not been explored. Here, we found that the occurrence of vessel co-option in bevacizumab-resistant CRCLM xenografts was associated with increased expression of fibroblast activation protein α (FAPα) in the co-opted hepatic stellate cells (HSCs), which was dramatically attenuated in HSC-specific conditional Fap-knockout mice bearing CRCLM allografts. Mechanistically, bevacizumab treatment induced hypoxia to upregulate the expression of fibroblast growth factor-binding protein 1 (FGFBP1) in tumor cells. Gain- or loss-of-function experiments revealed that the bevacizumab-resistant tumor cell-derived FGFBP1 induced FAPα expression by enhancing the paracrine FGF2/FGFR1/ERK1/-2/EGR1 signaling pathway in HSCs. FAPα promoted CXCL5 secretion in HSCs, which activated CXCR2 to promote the epithelial-mesenchymal transition of tumor cells and the recruitment of myeloid-derived suppressor cells. These findings were further validated in tumor tissues derived from patients with CRCLM. Targeting FAPα+ HSCs effectively disrupted the co-opted sinusoidal blood vessels and overcame bevacizumab resistance. Our study highlights the role of FAPα+ HSCs in vessel co-option and provides an effective strategy to overcome the vessel co-option-mediated bevacizumab resistance.
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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.