ArticleMolecular medicine reports2021
Porcupine inhibitor LGK‑974 inhibits Wnt/β‑catenin signaling and modifies tumor‑associated macrophages resulting in inhibition of the malignant behaviors of non‑small cell lung cancer cells.
Article in Molecular medicine reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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14 citing papers in PubMed, 28 citations in OpenAlex.
- An anaerobic pathogen rewires host metabolism to fuel oxidative growth in the inflamed gut.Cell · 2026Article
- Wnt signaling and the tumor microenvironment: implications for cancer progression and therapeutics.Oncogene · 2026Review
- Wnt signaling in cancer: from biomarkers to targeted therapies and clinical translation.Molecular cancer · 2025Review
- Oncogenic KRAS Mutations Confer a Unique Mechanotransduction Response to Peristalsis in Colorectal Cancer Cells.Molecular cancer research : MCR · 2025Article
- Porcupine expression promotes the progression of oral carcinogenesis.Neoplasia (New York, N.Y.) · 2025Article
- Wnt/β-catenin signaling in the development and therapeutic resistance of non-small cell lung cancer.Journal of translational medicine · 2024Review
- The genomic landscape of the immune system in lung cancer: present insights and continuing investigations.Frontiers in genetics · 2024Review
- Wnt Signaling and Therapeutic Resistance in Castration-Resistant Prostate Cancer.Current pharmacology reports · 2023Article
- Suppression of tumor cell lactate-generating signaling pathways eradicates murine PTEN/p53-deficient aggressive-variant prostate cancer via macrophage phagocytosis.bioRxiv : the preprint server for biology · 2023Article
- The role of Evi/Wntless in exporting Wnt proteins.Development (Cambridge, England) · 2023Review
- Wnt Signaling in the Phenotype and Function of Tumor-Associated Macrophages.Cancer research · 2023Article
- Targeting tumor-associated macrophage: an adjuvant strategy for lung cancer therapy.Frontiers in immunology · 2023Review
- Molecular Biomarkers and Signaling Pathways of Cancer Stem Cells in Colorectal Cancer.Technology in cancer research & treatmentReview
- Exacerbation of paclitaxel-induced neuropathic pain behaviors in breast tumor-bearing mice.Molecular painArticle
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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
Tumor‑associated macrophages (TAMs) are critical components of the tumor microenvironment that are tightly associated with malignancies in human cancers, including lung cancer. LGK‑974, a small molecular inhibitor of Wnt secretion, was reported to block Wnt/β‑catenin signaling and exert anti‑inflammatory effects by suppressing pro‑inflammatory gene expression in cancer cells. Although it was reported that Wnt/β‑catenin was critical in regulating TAMs, it is still largely unknown whether LGK‑974 regulates tumor malignancies by regulating TAMs. The present study firstly verified that the polarization of TAMs was regulated by LGK‑974. LGK‑974 increased M1 macrophage functional markers and decreased M2 macrophage functional markers. The addition of Wnt3a and Wnt5a, two canonical Wnt signaling inducers, reversed the decrease in M1 macrophage functional markers, including mannose receptor, IL‑10 and Arg1, by activating Wnt/β‑catenin signaling. Conditioned medium from LGK‑974‑modified TAMs inhibited the malignant behaviors in A549 and H1299 cells, including proliferation, colony formation and invasion, by blocking Wnt/β‑catenin signaling. LGK‑974‑modified TAMs blocked the cell cycle at the G
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