ArticleSignal transduction and targeted therapy2021
Mutant KRAS triggers functional reprogramming of tumor-associated macrophages in colorectal cancer.
Article in Signal transduction and targeted therapy, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers.
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Who cites it
60 citing papers in PubMed, 89 citations in OpenAlex.
- A Phase 1b/2 Study of the Anti-CD47 Antibody Magrolimab with Cetuximab in Patients with Colorectal Cancer and Other Solid Tumors.Targeted oncology · 2025Trial
- Lactate as a Master Regulator of Immune Suppression: From Metabolic Waste to Epigenetic Checkpoint in Colorectal Cancer.International journal of molecular sciences · 2026Review
- KRASScience advances · 2026Article
- RAS signaling at the crossroads of radioresistance and tumor immunity.Journal for immunotherapy of cancer · 2026Review
- Aspartate Transporter SLC1A3 Promotes Colorectal Cancer via MDM2-p53 Pathway and M2 Macrophage Polarization.Cancer science · 2026Article
- Macrophage-Derived PDGF-BB and GDF-15 Promote Drug Resistance in KRAS-Mutant Colorectal Cancer.bioRxiv : the preprint server for biology · 2026Article
- Multifunctional copper-based nanoparticles potentiate colorectal cancer immunotherapy via synergistic metabolic remodeling and cGAS-STING pathway activation.Journal of nanobiotechnology · 2026Article
- Mechanism of Yiqi Huoxue Granule in promoting angiogenesis of skin lesion tissue by increasing CSF2 to reduce mesenchymal stem cell apoptosis.Frontiers in pharmacology · 2026Article
- Targeting TREM2Cancer communications (London, England) · 2026Article
- RAS mutation status and immune microenvironment define distinct prognostic landscapes and predict chemotherapy benefit in pMMR colorectal cancer.Frontiers in immunology · 2026Article
- Metabolic symbiosis and competition: the dual nature of TAM-tumor cell cross-talk in tumor progression.Frontiers in oncology · 2026Review
- A comprehensive review of mechanisms underlying resistance to immune checkpoint inhibitors.Frontiers in immunology · 2026Review
- IL-6 as a central driver of immune evasion in PDAC: from IDO-mediated tolerance to multi-pathway immunosuppression.Frontiers in immunology · 2026Review
- AI-powered immune profiling from histopathology slides for chemo-radiotherapy outcome prediction in rectal cancer: a study using clinical trial and real-world cohorts.EBioMedicine · 2025Article
- Oncogenic KRAS mutations drive immune suppression through immune-related regulatory network and metabolic reprogramming.Cell death & disease · 2025Review
- Unraveling tumor cell‑tumor microenvironment crosstalk through antibody array technologies (Review).International journal of oncology · 2025Review
- Novel paradigms in KRAS targeting: Unveiling strategies to combat drug resistance.Chinese medical journal · 2025Review
- Crosstalk Between Metabolic Reprogramming and Epigenetic Modifications in Colorectal Cancer: Mechanisms and Clinical Applications.Current issues in molecular biology · 2025Review
- Mechanistic Foundations of KRAS-Driven Tumor Ecosystems: Integrating Crosstalk among Immune, Metabolic, Microbial, and Stromal Microenvironment.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Review
- Immune evasion in cancer: mechanisms and cutting-edge therapeutic approaches.Signal transduction and targeted therapy · 2025Review
Corrections and comments
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Oncogenic KRAS has been previously identified to act in a cell-intrinsic manner to modulate multiple biological functions of colorectal cancer (CRC). Here, we demonstrate a cell-extrinsic role of KRAS, where KRAS engages with the tumor microenvironment by functional reprogramming of tumor-associated macrophages (TAMs). In human CRC specimens, mutant KRAS positively correlates with the presence of TAMs. Mutationally activated KRAS in tumor cells reprograms macrophages to a TAM-like phenotype via a combination effect of tumor-derived CSF2 and lactate. In turn, KRAS-reprogrammed macrophages were shown to not only promote tumor progression but also induce the resistance of tumor cells to cetuximab therapy. Mechanistically, KRAS drives the production of CSF2 and lactate in tumor cells by stabilizing hypoxia-inducible factor-1α (HIF-1α), a transcription factor that controls the expression of CSF2 and glycolytic genes. Mutant KRAS increased the production of reactive oxygen species, an inhibitor of prolyl hydroxylase activity which decreases HIF-1α hydroxylation, leading to enhanced HIF-1α stabilization. This cell-extrinsic mechanism awards KRAS a critical role in engineering a permissive microenvironment to promote tumor malignancy, and may present new insights on potential therapeutic defense strategies against mutant KRAS tumors.
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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.