ArticleJournal of translational medicine2023
Upregulation of HMGB1 in tumor-associated macrophages induced by tumor cell-derived lactate further promotes colorectal cancer progression.
Article in Journal of translational medicine, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 46 citations in OpenAlex.
- HMGB1 Post-Translational Modifications in Epstein-Barr Virus-Associated Nasopharyngeal Carcinoma: Current Evidence, Emerging Mechanistic Concepts, and Unresolved Questions.International journal of molecular sciences · 2026Review
- EIF3H Modulates Glycolysis Through LDHA Stabilization in Triple-Negative Breast Cancer.Cancers · 2026Article
- Clonal Hematopoiesis in Colorectal Cancer: Mechanisms and Implications.Cancer medicine · 2026Review
- Clinical implications of lactylation modification in digestive system tumors (Review).Oncology letters · 2026Review
- METTL5 reprograms glycolytic metabolism and promotes non-small cell lung cancer progression by modifying PGAM1.Oncology letters · 2026Article
- Chemerin Promotes Oral Squamous Cell Carcinoma Progression via NLRP3-Mediated Pyroptosis and the GSDMD-N Pathway.International dental journal · 2026Article
- Histone lactylation modification promotes docetaxel resistance and tumor progression through CNN1-Mediated autophagy and cell cycle arrest in Castration-resistant prostate cancer.Cell death discovery · 2026Article
- Glucose metabolic reprogramming as a driver of immunosuppression in the tumour microenvironment.Clinical and translational medicine · 2026Review
- STAMBP drives colorectal cancer progression via CXCR4 deubiquitination and bone marrow-derived suppressor cell recruitment.Genes and immunity · 2026Article
- IOA-244, a novel p110δ PI3K inhibitor, blocks breast tumour progression on either mono- or combined-therapy.Cell death discovery · 2026Article
- Distribution and prognostic value of macrophages in colorectal cancer and adjacent mucosa in patient stages I-IIIWorld journal of gastroenterology · 2026Article
- DCUN1D5 promotes the proliferation and migration of colorectal cancer tumors in vitro and in vivo.Cancer cell international · 2026Article
- The Role of Jianpi Jiedu Recipe in Modulating the CRC Microenvironment.Combinatorial chemistry & high throughput screening · 2026Article
- Nanodynamic Therapy in Colorectal Cancer: Engineering Precision Immunotherapy and Multimodal Synergy.International journal of nanomedicine · 2026Review
- UPF1-dependent glycolysis driven by LINC00887 facilitates macrophage M2 polarization in clear cell renal cell carcinoma.Frontiers in immunology · 2026Article
- The role of extracellular vesicles in the transport and regulation of novel inflammatory mediators in IBD and its associated CRC.Frontiers in cell and developmental biology · 2026Review
- TIM-3 blockade enhances ex vivo stimulated allogeneic NK cell therapy for relapsed murine neuroblastoma after hematopoietic cell transplant.Journal for immunotherapy of cancer · 2025Article
- Lactate at the crossroads of tumor metabolism and immune escape: a new frontier in cancer therapy.Journal of translational medicine · 2025Review
- Downregulation of KHSRP enhances carboplatin sensitivity in non-small cell lung cancer.Hereditas · 2025Article
- Lactate and lactylation: molecular insights into histone and non-histone lactylation in tumor progression, tumor immune microenvironment, and therapeutic strategies.Biomarker research · 2025Review
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundLactate accumulation leads to an acidic tumor microenvironment (TME), in turn promoting colorectal cancer (CRC) progression. Tumor-associated macrophages (TAMs) are the predominant cells in TME. This study aimed to reveal the regulation mechanism of CRC cell-derived lactate on TAMs and explore the mechanism underlying lactate accumulation-induced aggravation in CRC.
methodsCell growth and metastasis were evaluated by colony formation, Transwell, and wound healing assays. Western blot and RT-qPCR were applied to determine the protein and mRNA expression. Flow cytometry was used to analyze the polarization state and apoptotic rate of macrophages induced in THP-1 cells. The lactate in the cell supernatant was quantified using an ELISA kit. Immunofluorescence was performed to visualize the location of High Mobility Group Box 1 (HMGB1). H&E and Ki67 staining assays were used to assess tumorigenesis in nude mice bearing ectopic tumors.
resultsCell growth and metastasis were promoted in the hypoxic CRC cells. The hypoxic cell supernatant stimulated the M2-type polarization of macrophages. The lactate level increased in hypoxic cancer cells. However, the inhibition of lactate using 3-hydroxy-butyrate (3-OBA) reversed the effects of hypoxia. Also, macrophages showed no promoting effect on cancer cell growth and migration in the presence of 3-OBA. HMGB1 was secreted into the extracellular space of lactate-induced macrophages, further enhancing the malignant behaviors of cancer cells. ERK, EMT, and Wnt signaling pathways were activated in cancer cells due to HMGB1 upregulation.
conclusionsThe lactate metabolized by cancer cells stimulated M2 polarization and HMGB1 secretion by macrophages, aggravating the carcinogenic behaviors of cancer cells.
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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.