ArticleCell death & disease2023
Tumor-associated macrophages confer colorectal cancer 5-fluorouracil resistance by promoting MRP1 membrane translocation via an intercellular CXCL17/CXCL22-CCR4-ATF6-GRP78 axis.
Article in Cell death & disease, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 44 citations in OpenAlex.
- Mechanisms and advances of drug resistance in colorectal cancer: A systematic overview of multi-layered regulatory networks.Translational oncology · 2026Review
- Targeting CDK2 and AURKA with Cerevisterol fromInternational journal of molecular sciences · 2026Article
- Personalized chemotherapy guidance using patient-derived scaffolds from peritoneal colorectal metastases.Experimental hematology & oncology · 2026Article
- Tumor-associated macrophages suppress estrogen receptor-β expression in triple-negative breast cancer through the PI3K/AKT pathway.Experimental and therapeutic medicine · 2026Article
- Remodeling the tumor immune microenvironment: mechanisms of crosstalk between regulated cell death macrophages.Frontiers in immunology · 2026Review
- Role of mucosal chemokines in the development of tissue-resident CD4Frontiers in immunology · 2026Review
- Implications of Heterotypic Cell Fusion in Cancer.Advances in experimental medicine and biology · 2026Review
- GIPC1 Restrains the Progression and Chemoresistance of Colorectal Cancer by Regulating TTC7B/mTOR/NF-κB Axis.International journal of biological sciences · 2026Article
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- Association of EnterotoxigenicCancers · 2025Article
- Nanoparticle-Based Delivery Strategies for Combating Drug Resistance in Cancer Therapeutics.Cancers · 2025Review
- Stress Management: How the Endoplasmic Reticulum Mitigates Protein Misfolding and Oxidative Stress by the Dual Role of Glutathione Peroxidase 8.Biomolecules · 2025Review
- Chemotherapy-induced macrophage CXCL7 expression drives tumor chemoresistance via the STAT1/PHGDH-serine metabolism axis and SAM paracrine feedback to M2 polarization.Cell death & disease · 2025Article
- Natural Alternatives in the Treatment of Colorectal Cancer: A Mechanisms Perspective.Biomolecules · 2025Review
- Article
- GRP78 as a potential therapeutic target in cancer treatment: an updated review of its role in chemoradiotherapy resistance of cancer cells.Medical oncology (Northwood, London, England) · 2025Review
- Cancer stem cells and tumor-associated macrophages as mates in tumor progression: mechanisms of crosstalk and advanced bioinformatic tools to dissect their phenotypes and interaction.Frontiers in immunology · 2025Review
- Unveiling the tumor microenvironment in colorectal cancer therapeutic resistance.Frontiers in cell and developmental biology · 2025Review
- The role of glycan-lectin interactions in the tumor microenvironment: immunosuppression regulators of colorectal cancer.American journal of cancer research · 2025Review
- M2-like Macrophages-derived CCL17 Promotes Esophageal Squamous Cell Carcinoma Metastasis and Stemness via Activating CCR4-mediated ERK/PD-L1 Pathway.Current molecular medicine · 2025Article
Corrections and comments
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Authors and funding
14 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Chemotherapy represents a major type of clinical treatment against colorectal cancer (CRC). Aberrant drug efflux mediated by transporters acts as a key approach for tumor cells to acquire chemotherapy resistance. Increasing evidence implies that tumor-associated macrophages (TAMs) play a pivotal role in both tumorigenesis and drug resistance. Nevertheless, the specific mechanism through which TAMs regulate drug efflux remains elusive. Here, we discovered that TAMs endow CRC cells with resistance to 5-fluorouracil (5-FU) treatment via a cell-cell interaction-mediated MRP1-dependent drug efflux process. Mechanistically, TAM-secreted C-C motif chemokine ligand 17 (CCL17) and CCL22, via membrane receptor CCR4, activated the PI3K/AKT pathway in CRC tumor cells. Specifically, phosphorylation of AKT inactivated IP3R and induced calcium aggregation in the ER, resulting in the activation of ATF6 and upregulation of GRP78. Accordingly, excessive GRP78 can interact with MRP1 and promote its translocation to the cell membrane, causing TAM-induced 5-FU efflux. Taken together, our results demonstrated that TAMs promote CRC chemotherapy resistance via elevating the expression of GRP78 to promote the membrane translocation of MRP1 and drug efflux, providing direct proof for TAM-induced drug resistance.
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