ArticleProceedings of the National Academy of Sciences of the United States of America2010
Synergistic antitumor effects of combined cathepsin B and cathepsin Z deficiencies on breast cancer progression and metastasis in mice.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 93 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
93 citing papers in PubMed, 175 citations in OpenAlex.
- Prognostic and predictive value of cathepsin X in serum from colorectal cancer patients.BMC cancer · 2014Trial
- The role of Cathepsin S as a marker of prognosis and predictor of chemotherapy benefit in adjuvant CRC: a pilot study.British journal of cancer · 2011Trial
- Isoleucyl-tRNA synthetase 1 mutation impairs pulmonary surfactant homeostasis by disrupting alveolar macrophage function.Respiratory research · 2026Article
- Cathepsin Z/X: Breaking Down the Known and Unknown.International journal of molecular sciences · 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
- Cell-line specific role of Cathepsin B in triple-negative breast cancer growth, invasion and response to chemotherapy.bioRxiv : the preprint server for biology · 2025Article
- Cathepsin Z is a conserved susceptibility factor underlying tuberculosis severity.PLoS biology · 2025Article
- Machine learning unravels the mysteries of glioma typing and treatment.Biochemistry and biophysics reports · 2025Article
- Prognostic and immunological implications of cathepsin Z overexpression in prostate cancer.Frontiers in immunology · 2025Article
- PKM2 orchestrates tumor progression via metabolic reprogramming and MDSCs-mediated immune suppression in the tumor microenvironment.Frontiers in immunology · 2025Review
- Cathepsin X deficiency alters the processing and localisation of cathepsin L and impairs cleavage of a nuclear cathepsin L substrate.Biological chemistry · 2024Article
- Ruthenium-Cathepsin Inhibitor Conjugates for Green Light-Activated Photodynamic Therapy and Photochemotherapy.Inorganic chemistry · 2024Article
- The Role of Cysteine Protease Cathepsins B, H, C, and X/Z in Neurodegenerative Diseases and Cancer.International journal of molecular sciences · 2023Review
- Smart Delivery Systems Responsive to Cathepsin B Activity for Cancer Treatment.Pharmaceutics · 2023Review
- Cathepsin B Gene Knockout Improves Behavioral Deficits and Reduces Pathology in Models of Neurologic Disorders.Pharmacological reviews · 2022Review
- Histologically resolved multiomics enables precise molecular profiling of human intratumor heterogeneity.PLoS biology · 2022Article
- Lysosomal peptidases-intriguing roles in cancer progression and neurodegeneration.FEBS open bio · 2022Review
- Differential regulation of progranulin derived granulin peptides.Molecular neurodegeneration · 2022Article
- Evaluation of novel cathepsin-X inhibitors in vitro and in vivo and their ability to improve cathepsin-B-directed antitumor therapy.Cellular and molecular life sciences : CMLS · 2022Article
33 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The lysosomal cysteine proteases cathepsin B (Ctsb) and cathepsin Z (Ctsz, also called cathepsin X/P) have been implicated in cancer pathogenesis. Compensation of Ctsb by Ctsz in Ctsb (-/-) mice has been suggested. To further define the functional interplay of these proteases in the context of cancer, we generated Ctsz null mice, crossed them with Ctsb-deficient mice harboring a transgene for the mammary duct-specific expression of polyoma middle T oncogene (PymT), and analyzed the effects of single and combined Ctsb and Ctsz deficiencies on breast cancer progression. Single Ctsb deficiency resulted in delayed detection of first tumors and reduced tumor burden, whereas Ctsz-deficient mice had only a prolonged tumor-free period. However, only a trend toward reduced metastatic burden without statistical significance was detected in both single mutants. Strikingly, combined loss of Ctsb and Ctsz led to additive effects, resulting in significant and prominent delay of early and advanced tumor development, improved histopathologic tumor grading, as well as a 70% reduction in the number of lung metastases and an 80% reduction in the size of these metastases. We conclude that the double deficiency of Ctsb and Ctsz exerts significant synergistic anticancer effects, whereas the single deficiencies demonstrate at least partial reciprocal compensation.
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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.