ArticleGenes & development2014
Distinct functions of macrophage-derived and cancer cell-derived cathepsin Z combine to promote tumor malignancy via interactions with the extracellular matrix.
Article in Genes & development, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 86 papers.
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Who cites it
86 citing papers in PubMed, 115 citations in OpenAlex.
- Plasma proteomic profiling in dogs with pheochromocytoma.Journal of veterinary internal medicine · 2026Article
- Targeting lysosome-dependent cell death in cancer: towards therapeutic strategies.Biomarker research · 2026Review
- Macrophage-derived CTSZ promotes prostate cancer progression via αVβ3 integrin-mediated activation of the AKT/FOXO1/JUNB signaling axis.Cancer cell international · 2026Article
- CTSZ-dependent anoikis resistance enhances malignant characters of glioblastoma via NF-κB signaling.iScience · 2026Article
- Cathepsin Z/X: Breaking Down the Known and Unknown.International journal of molecular sciences · 2026Review
- The Lysosome-Cathepsin Axis in Pancreatic Cancer: Mechanisms of Stromal Remodeling, Immune Evasion, and Therapy Resistance.Biomolecules · 2026Review
- Loss of Cathepsin Z enhances pro-inflammatory macrophage responses and promotes tissue regeneration.Disease models & mechanisms · 2026Article
- Probing the activity of cysteine cathepsins in inflammatory bowel diseases.Scientific reports · 2025Article
- Heterogeneity of Extracellular Vesicles and Non-Vesicular Nanoparticles in Glioblastoma.Journal of extracellular vesicles · 2025Article
- The CTSZ-TRA2A-IL32 axis defines a targetable macrophage-dependent pathway in metastatic prostate cancer.Journal of translational medicine · 2025Article
- A new paradigm of islet adaptations in human pregnancy: insights from immunohistochemistry and proteomics.Nature communications · 2025Article
- Metastatic heterogeneity in pancreatic cancer: mechanisms and opportunities for targeted intervention.The Journal of clinical investigation · 2025Review
- The Role of the Tumor Microenvironment in Gastroenteropancreatic Neuroendocrine Tumors.International journal of molecular sciences · 2025Review
- The role of immune cells phenotype in neuroendocrine tumors development.Discover oncology · 2025Article
- Machine learning unravels the mysteries of glioma typing and treatment.Biochemistry and biophysics reports · 2025Article
- Are cathepsins a risk factor for papillary thyroid carcinoma? A bidirectional two-sample mendelian randomization analysis.European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery · 2025Article
- Mendelian Randomization Analyses Reveal the Causal Effect of Cathepsin Z on the Risk of Different Subtypes of Thyroid Cancer.International journal of endocrinology · 2025Article
- Harnessing Macrophages in Cancer Therapy: from Immune Modulators to Therapeutic Targets.International journal of biological sciences · 2025Review
- Prognostic and immunological implications of cathepsin Z overexpression in prostate cancer.Frontiers in immunology · 2025Article
- Investigating the role of cathepsins in breast cancer progression: a Mendelian randomization study.Frontiers in oncology · 2025Article
26 more citing papers are in PubMed but not listed here.
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Authors and funding
12 authors at 3 institutions in 2 countries.
Funding
Abstract
During the process of tumor progression, cancer cells can produce the requisite growth- and invasion-promoting factors and can also rely on noncancerous cells in the tumor microenvironment as an alternative, cell-extrinsic source. However, whether the cellular source influences the function of such tumor-promoting factors remains an open question. Here, we examined the roles of the cathepsin Z (CtsZ) protease, which is provided by both cancer cells and macrophages in pancreatic neuroendocrine tumors in humans and mice. We found that tumor proliferation was exclusively regulated by cancer cell-intrinsic functions of CtsZ, whereas tumor invasion required contributions from both macrophages and cancer cells. Interestingly, several of the tumor-promoting functions of CtsZ were not dependent on its described catalytic activity but instead were mediated via the Arg-Gly-Asp (RGD) motif in the enzyme prodomain, which regulated interactions with integrins and the extracellular matrix. Together, these results underscore the complexity of interactions within the tumor microenvironment and indicate that cellular source can indeed impact molecular function.
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Registered trials
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.