ArticleGastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association2022
CAF promotes chemoresistance through NRP2 in gastric cancer.
Article in Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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33 citing papers in PubMed, 49 citations in OpenAlex.
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- Therapy-educated fibroblast states link treatment pressure to residual disease and acquired resistance in gastric cancer.Frontiers in immunology · 2026Review
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- Stemness signatures reflect prognostic disturbances in gastric cancer.World journal of gastrointestinal oncology · 2025Article
- Patient-Derived Gastric Cancer Assembloid Model Integrating Matched Tumor Organoids and Stromal Cell Subpopulations.Cancers · 2025Article
- YBX1 promotes 5-Fluorouracil resistance in gastric cancer via m5C-dependent ATG9A mRNA stabilization through autophagy.Oncogene · 2025Article
- Hotspots and frontiers of the relationship between gastric cancer and cancer-associated fibroblasts: a bibliometric analysis.Frontiers in oncology · 2025Article
- Reversal of chemotherapy resistance in gastric cancer with traditional Chinese medicine as sensitizer: potential mechanism of action.Frontiers in oncology · 2025Review
- Autonomic nervous system development-related signature as a novel predictive biomarker for immunotherapy in pan-cancers.Frontiers in immunology · 2025Article
- ALKBH4 impedes 5-FU Sensitivity through suppressing GSDME induced pyroptosis in gastric cancer.Cell death & disease · 2024Article
- Pathomics and single-cell analysis of papillary thyroid carcinoma reveal the pro-metastatic influence of cancer-associated fibroblasts.BMC cancer · 2024Article
- Pan-Cancer Analysis of the Prognostic and Immunological Role of SEMA7A.International journal of general medicine · 2024Article
- Article
- Cancer-associated fibroblasts: protagonists of the tumor microenvironment in gastric cancer.Frontiers in molecular biosciences · 2024Review
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundFibroblasts are the predominant cell type in the stroma of tumor, and cancer-associated fibroblasts (CAFs) promote cancer chemoresistance by secreting various bioactive molecules. However, the differential expression between CAFs and normal fibroblasts (NFs) and how can CAFs uniquely impact cancer cells are still unexplored.
methodsPrimary CAFs and NFs were cultured from gastric cancer specimens, and their variant expression was analyzed by RNA-sequencing. Chemoresistance was evaluated by measuring cell viability, apoptosis, and 3D-coculture techniques.
resultsCAFs were isolated from gastric cancers and defined by specific cell-surface markers. CAFs decreased the sensitivity of gastric cancer cells to 5-FU. RNA-sequencing showed that CAFs expressed a higher level of NRP2 than NFs. And the high expression of NRP2 was correlated with worse oncological outcomes in gastric cancer patients. Further study showed that the knockdown of NRP2 eradicated the resistance to 5-FU. And the secretion of stromal cell-derived factor-1 (SDF-1) was reduced following NRP2 knockdown. Furthermore, we found that the increased sensitivity to 5-FU was induced by DNA damage. And this process was mediated by predominant effectors of the Hippo pathway, YAP/TAZ.
conclusionsThe present study indicated that CAFs within gastric cancers promote chemoresistance through the expression of NRP2. The secretion of SDF-1 that mediated by VEGF/NRP2 signaling in CAFs and the activation of Hippo pathway in cancer cells in large part participated in this project.
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