ArticleJournal of experimental & clinical cancer research : CR2017
MIF/CD74 axis is a target for novel therapies in colon carcinomatosis.
Article in Journal of experimental & clinical cancer research : CR, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. It is linked to trial NCT04001725 (Efficacy of metfOrmin in PrevenTIng Glucocorticoid-induced Diabetes in Melanoma, breAst or Lung Cancer Patients With Brain Metastases), which is not on this map. Cited by 39 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Efficacy of metfOrmin in PrevenTIng Glucocorticoid-induced Diabetes in Melanoma, breAst or Lung Cancer Patients With Brain Metastases: the Phase II OPTIMAL Study
Who cites it
39 citing papers in PubMed, 74 citations in OpenAlex.
- Dissecting Intra-Tumoral Changes Following Immune Checkpoint Blockades in Intrahepatic CholangiocarcinomaFrontiers in immunology · 2022Trial
- Correction: MIF/CD74 axis is a target for novel therapies in colon carcinomatosis.Journal of experimental & clinical cancer research : CR · 2026Article
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- Screening and identification of biomarkers in tumor-educated platelets for non-small cell lung cancer.BMC cancer · 2026Article
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- Constructing a protein-protein interaction network for autoimmune liver diseases by integrating pQTL, rQTL, and mediation analyses.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Single-cell and spatial transcriptomics reveal TNC-positive cancer-associated fibroblasts that mediate immunosuppression and promote tumor progression in basal cell carcinoma.Journal of translational medicine · 2025Article
- Targeting macrophage migration inhibitory factor as a potential therapeutic strategy in colorectal cancer.Oncogenesis · 2025Article
- Review
- Efferocytosis-associated genes serve as prognostic biomarkers for pancreatic ductal adenocarcinoma and identify P2RY6 as a therapeutic target.Frontiers in immunology · 2025Article
- Exploration of the Roles and Mechanisms Between Tumor-Infiltrating Lymphocytes and Hepatocellular Carcinoma Based on Single-Cell Transcriptomics.International journal of genomics · 2025Article
- A combinatorial culture strategy to develop pseudomyxoma peritonei organoid models.Journal of surgical oncology · 2024Article
- Sulfatide imaging identifies tumor cells in colorectal cancer peritoneal metastases.Cancer & metabolism · 2024Article
- Blocking the MIF-CD74 axis augments radiotherapy efficacy for brain metastasis in NSCLC via synergistically promoting microglia M1 polarization.Journal of experimental & clinical cancer research : CR · 2024Article
- Metformin: From Diabetes to Cancer-Unveiling Molecular Mechanisms and Therapeutic Strategies.Biology · 2024Review
- Unraveling intratumoral complexity in metastatic dermatofibrosarcoma protuberans through single-cell RNA sequencing analysis.Cancer immunology, immunotherapy : CII · 2023Article
- Infection and inflammation stimulate expansion of a CD74The EMBO journal · 2023Article
- Utilizing Patient-Derived Organoids in the Management of Colorectal Cancer with Peritoneal Metastases: A Review of Current Literature.Journal of gastrointestinal cancer · 2023Review
- Decellularized extracellular matrix as scaffold for cancer organoid cultures of colorectal peritoneal metastases.Journal of molecular cell biology · 2023Article
- An Immune-Related Genetic Feature Depicted the Heterogeneous Nature of Lung Adenocarcinoma and Squamous Cell Carcinoma and Their Distinctive Predicted Drug Responses.Oxidative medicine and cellular longevity · 2022Article
Corrections and comments
- Erratum issued
Authors and funding
17 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundStrategies aimed at obtaining a complete cytoreduction are needed to improve long-term survival for patients with colorectal cancer peritoneal carcinomatosis (CRC-pc).
methodsWe established organoid models from peritoneal metastases of two naïve CRC patients. A standard paraffin inclusion was conducted to compare their 3D structure and immunohistochemical profile with that of the corresponding surgical samples. RNA expression levels of the CRC stem cell marker LGR5 was measured by in situ hybridization. The secretome of organoids was profiled by mass spectrometry. Energy homeostasis of organoids was interfered with 4-IPP and metformin. Biochemical and metabolic changes after drug treatments were investigated by western blot and mass spectrometry. Mitochondria impairment was evaluated by electron microscopy and mitotraker staining.
resultsThe two organoids recapitulated their corresponding clinical samples in terms of 3D structure and immmunoistochemical profile and were positive for the cancer stem cells marker LGR5. Proteomic analyses of organoids highlighted their strong dependence on energy producing pathways, which suggest that their targeting could be an effective therapeutic approach. To test this hypothesis, we treated organoids with two drugs that target metabolism acting on AMP-activated protein kinase (AMPK), the main regulator of cellular energy homeostasis, which may act as metabolic tumour suppressor in CRC. Organoids were treated with 4-IPP, an inhibitor of MIF/CD74 signalling axis which activates AMPK function, or metformin that inhibits mitochondrial respiratory chain complex I. As a new finding we observed that treatment with 4-IPP downregulated AMPK signalling activity, reduced AKT phosphorylation and activated a JNK-mediated stress-signalling response, thus generating mitochondrial impairment and cell death. Metformin treatment enhanced AMPK activation, decreasing the activity of the anabolic factors ribosomal protein S6 and p4EBP-1 and inducing mitochondrial depolarization.
conclusionWe provide evidence that the modulation of AMPK activity may be a strategy for targeting metabolism of CRC-pc organoids.
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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.