ArticleMolecular oncology2017
Kallikrein-related peptidase 4 induces cancer-associated fibroblast features in prostate-derived stromal cells.
Article in Molecular oncology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 25 citations in OpenAlex.
- RNA methyltransferase 3 drives pancreatic acinar cell carcinoma growth and is a therapeutic target.Signal transduction and targeted therapy · 2026Article
- Inhibition of Growth and Induction of Apoptosis of Human Prostate Cancer Cells by Enzymatic Blockage of Kallikreins.Prostate cancer · 2026Article
- Article
- METTL16 promotes progression of clear cell renal cell carcinoma via up-regulating N6-methyladenosine modification of KLK4 mRNA.Molecular and cellular biochemistry · 2025Article
- The multifaceted role of the stroma in the healthy prostate and prostate cancer.Journal of translational medicine · 2024Review
- Hypoxic Regulation of the KLK4 Gene in two Different Prostate Cancer Cells Treated with TGF- β.Cell biochemistry and biophysics · 2024Article
- Epithelial-Mesenchymal Transition: A Fundamental Cellular and Microenvironmental Process in Benign and Malignant Prostate Pathologies.Biomedicines · 2024Review
- Role of actin-binding proteins in prostate cancer.Frontiers in cell and developmental biology · 2024Review
- "Stromal cells in prostate cancer pathobiology: friends or foes?"British journal of cancer · 2023Review
- Spatiotemporal analysis of tumour-infiltrating immune cells in biliary carcinogenesis.British journal of cancer · 2022Article
- Prostate Cancer Tumor Stroma: Responsibility in Tumor Biology, Diagnosis and Treatment.Cancers · 2022Review
- Remodelling of the tumour microenvironment by the kallikrein-related peptidases.Nature reviews. Cancer · 2022Review
- Role of Serine Proteases at the Tumor-Stroma Interface.Frontiers in immunology · 2022Review
- KLK4T2 Is a Hormonally Regulated Transcript from theInternational journal of molecular sciences · 2021Article
- A KLK4 proteinase substrate capture approach to antagonize PAR1.Scientific reports · 2021Article
- 5-Hydroxymethylcytosine signature in circulating cell-free DNA as a potential diagnostic factor for early-stage colorectal cancer and precancerous adenoma.Molecular oncology · 2021Article
- KLK4 Induces Anti-Tumor Effects in Human Xenograft Mouse Models of Orthotopic and Metastatic Prostate Cancer.Cancers · 2020Article
- Review
- Determinants and Functions of CAFs Secretome During Cancer Progression and Therapy.Frontiers in cell and developmental biology · 2020Review
- Potent, Selective, and Cell-Penetrating Inhibitors of Kallikrein-Related Peptidase 4 Based on the Cyclic Peptide MCoTI-II.ACS medicinal chemistry letters · 2018Article
Corrections and comments
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Authors and funding
13 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The reciprocal communication between cancer cells and their microenvironment is critical in cancer progression. Although involvement of cancer-associated fibroblasts (CAF) in cancer progression is long established, the molecular mechanisms leading to differentiation of CAFs from normal fibroblasts are poorly understood. Here, we report that kallikrein-related peptidase-4 (KLK4) promotes CAF differentiation. KLK4 is highly expressed in prostate epithelial cells of premalignant (prostatic intraepithelial neoplasia) and malignant lesions compared to normal prostate epithelia, especially at the peristromal interface. KLK4 induced CAF-like features in the prostate-derived WPMY1 normal stromal cell line, including increased expression of alpha-smooth muscle actin, ESR1 and SFRP1. KLK4 activated protease-activated receptor-1 in WPMY1 cells increasing expression of several factors (FGF1, TAGLN, LOX, IL8, VEGFA) involved in prostate cancer progression. In addition, KLK4 induced WPMY1 cell proliferation and secretome changes, which in turn stimulated HUVEC cell proliferation that could be blocked by a VEGFA antibody. Importantly, the genes dysregulated by KLK4 treatment of WPMY1 cells were also differentially expressed between patient-derived CAFs compared to matched nonmalignant fibroblasts and were further increased by KLK4 treatment. Taken together, we propose that epithelial-derived KLK4 promotes tumour progression by actively promoting CAF differentiation in the prostate stromal microenvironment.
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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.