ArticleCells2022
KLK6/PAR1 Axis Promotes Tumor Growth and Metastasis by Regulating Cross-Talk between Tumor Cells and Macrophages.
Article in Cells, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 17 citations in OpenAlex.
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- Single-cell analyses unravel ecosystem dynamics and intercellular crosstalk during gallbladder cancer malignant transformation.Hepatology communications · 2025Article
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- Levodopa-induced dyskinesia: brain iron deposition as a new hypothesis.Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine · 2024Review
- Kallikrein-Related Peptidase 6 Contributes to Murine Intestinal Tumorigenesis Driven by a MutantCancers · 2024Article
- Protective Effects of Crotonis Semen Extract against Sepsis through NF-κB Pathway Inhibition.International journal of molecular sciences · 2024Article
- Recombinant hirudin and PAR-1 regulate macrophage polarisation status in diffuse large B-cell lymphoma.BMC biotechnology · 2024Article
- SCSMD: Single Cell Consistent Clustering based on Spectral Matrix Decomposition.Briefings in bioinformatics · 2024Article
- Crosstalk between cancer cells and macrophages promotes OSCC cell migration and invasion through a CXCL1/EGF positive feedback loop.Discover oncology · 2024Article
- The endoplasmic reticulum stress-related genes and molecular typing predicts prognosis and reveals characterization of tumor immune microenvironment in lung squamous cell carcinoma.Discover oncology · 2024Article
- Impaired activation of plasmacytoid dendritic cellsFrontiers in immunology · 2023Article
Corrections and comments
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Authors and funding
14 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Kallikrein-related peptidase (KLK)6 is associated with inflammatory diseases and neoplastic progression. KLK6 is aberrantly expressed in several solid tumors and regulates cancer development, metastatic progression, and drug resistance. However, the function of KLK6 in the tumor microenvironment remains unclear. This study aimed to determine the role of KLK6 in the tumor microenvironment. Here, we uncovered the mechanism underlying KLK6-mediated cross-talk between cancer cells and macrophages. Compared with wild-type mice, KLK6-/- mice showed less tumor growth and metastasis in the B16F10 melanoma and Lewis lung carcinoma (LLC) xenograft model. Mechanistically, KLK6 promoted the secretion of tumor necrosis factor-alpha (TNF-α) from macrophages via the activation of protease-activated receptor-1 (PAR1) in an autocrine manner. TNF-α secreted from macrophages induced the release of the C-X-C motif chemokine ligand 1 (CXCL1) from melanoma and lung carcinoma cells in a paracrine manner. The introduction of recombinant KLK6 protein in KLK6-/- mice rescued the production of TNF-α and CXCL1, tumor growth, and metastasis. Inhibition of PAR1 activity suppressed these malignant phenotypes rescued by rKLK6 in vitro and in vivo. Our findings suggest that KLK6 functions as an important molecular link between macrophages and cancer cells during malignant progression, thereby providing opportunities for therapeutic intervention.
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