ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2025
Targeting MAPK14 by Lobeline Upregulates Slurp1-Mediated Inhibition of Alternative Activation of TAM and Retards Colorectal Cancer Growth.
Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers, 1 of them a synthesis that pooled it.
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Who cites it
22 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Meta-Analysis and Topological Perturbation in Interactomic Network for Antiopioid Addiction Drug Repurposing.Journal of chemical information and modeling · 2025Pooled it
- DT-TRAP enables accurate target recognition via simplified dosing and low-temperature incubation.Journal of pharmaceutical analysis · 2026Article
- Tumor Microenvironment-on-a-Chip: Construction and Application in Traditional Chinese Medicine Anti-Tumor Therapy.Biosensors · 2026Review
- Recent advances in proteomic strategies for target identification of traditional Chinese medicine.Journal of pharmaceutical analysis · 2026Review
- Identification and Prognostic Analysis of Immune-Related Genes Co-Regulated by Key Histone Modifications in Breast Cancer.Current issues in molecular biology · 2026Article
- Targeting tumor-associated macrophages through phytochemicals: a promising strategy for cold tumor therapy.Chinese medicine · 2026Review
- Immediate tumor killing and long-term anti-tumor immunoreaction induced by Bufalin-loaded phototherapeutic Janus membrane in CRC postoperative therapy.Materials today. Bio · 2026Article
- PARP inhibitors restore NK cell function via secretory crosstalk with tumor cells in prostate cancer.The Journal of clinical investigation · 2026Article
- An integrative analysis reveals the mechanism of plastic stabilizers inducing breast cancer.PLoS computational biology · 2026Article
- Plant-Derived Bioactive Compounds in Inflammation-Related Cancers: Mechanisms and Therapeutic Potential.Plants (Basel, Switzerland) · 2026Review
- SLC39A10 drives M2 macrophage polarization and gastric cancer progression through the MAPK14(p38α) pathway.iScience · 2026Article
- Nanodelivery of Traditional Chinese Medicine Monomers: An Emerging Strategy to Reprogram the Immunosuppressive Tumor Microenvironment.International journal of nanomedicine · 2026Review
- TCM herb pairs regulate breast cancer TME heterogeneous mechanisms in immune, vascular, and stromal compartments.Frontiers in pharmacology · 2026Review
- Recent advances in drug repurposing for cancer immunomodulation emerging strategies, mechanistic insights, and clinical translation.Frontiers in oncology · 2026Review
- Modulation of stress granules by lobeline increases cell death in hypoxia and impacts the ability of glioblastoma cells to secrete extracellular vesicles.Cell death discovery · 2025Article
- Extracellular matrix dynamics in tumor immunoregulation: from tumor microenvironment to immunotherapy.Journal of hematology & oncology · 2025Review
- PTM-centered therapy in malignant tumors: A new story of colchicine.Acta pharmaceutica Sinica. B · 2025Article
- Marine-Derived Yaequinolone Derivative CHNQD-02792 Suppresses Colorectal Cancer Cell Proliferation and Induces Apoptosis via MAPK Pathway Modulation.Marine drugs · 2025Article
- Targeting MAPK14 by Lobeline Upregulates Slurp1-Mediated Inhibition of Alternative Activation of TAM and Retards Colorectal Cancer Growth.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- SLC40A1-mediated positive feedback loop with M1 macrophages suppresses epithelial ovarian cancer progression.Frontiers in immunology · 2025Article
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Authors and funding
16 authors.
Funding
Abstract
Colorectal cancer (CRC) usually creates an immunosuppressive microenvironment, thereby hindering immunotherapy response. Effective treatment options remain elusive. Using scRNA-seq analysis in a tumor-bearing murine model, it is found that lobeline, an alkaloid from the herbal medicine lobelia, promotes polarization of tumor-associated macrophages (TAMs) toward M1-like TAMs while inhibiting their polarization toward M2-like TAMs. Additionally, lobeline upregulates mRNA expression of secreted Ly-6/UPAR-related protein 1 (Slurp1) in cancer cells. The inhibitory effects of lobeline on tumor load and TAM polarization are almost completely eliminated when Slurp1-deficient MC38 cells are subcutaneously injected into mice, suggesting that lobeline exerts an antitumor effect in a Slurp1-dependent manner. Furthermore, using target-responsive accessibility profiling, MAPK14 is identified as the direct target protein of lobeline. Mechanistically, upon binding to MAPK14 in colon cancer cells, lobeline prevents nuclear translocation of MAPK14, resulting in decreased levels of phosphorylated p53. Consequently, negative transcriptional regulation of SLURP1 by p53 is suppressed, leading to enhanced transcription and secretion of SLURP1. Finally, combination therapy using lobeline and anti-PD1 exhibits stronger antitumor effects. Taken together, these findings suggest that remodeling the immunosuppressive microenvironment using small-molecule lobeline may represent a promising therapeutic strategy for CRC.
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