ArticleInternational journal of cancer2016
Cathepsin L inactivation leads to multimodal inhibition of prostate cancer cell dissemination in a preclinical bone metastasis model.
Article in International journal of cancer, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 56 citations in OpenAlex.
- Presurgical weight loss affects tumour traits and circulating biomarkers in men with prostate cancer.British journal of cancer · 2017Trial
- A deep learning and large language hybrid workflow for omics interpretation.Nature biomedical engineering · 2026Article
- Cathepsin L as a Driver of Tumour Invasion and a Novel Therapeutic Target in Ovarian Cancer.Cancers · 2026Review
- Cathepsin Inhibitor Suppresses the Growth of Ectopic Hepatocellular Carcinoma Tumors in Mouse Models.ACS pharmacology & translational science · 2026Article
- Cathepsins in prostate cancer: multifunctional regulators in tumor progression and therapeutic prospects-a narrative review.Translational andrology and urology · 2026Review
- CTSL loss leads to anti-PD-1 immunotherapy resistance in lung cancer by suppressing the anti-tumor function of peripheral CD8Frontiers in immunology · 2026Article
- Development of a prognostic risk model for predicting biochemical recurrence-free survival in patients with prostate cancer based on lysine acetylation.Translational andrology and urology · 2025Article
- Antibody-peptide conjugates deliver covalent inhibitors blocking oncogenic cathepsins.Nature chemical biology · 2024Article
- Disturbed intracellular folate homeostasis impairs autophagic flux and increases hepatocytic lipid accumulation.BMC biology · 2024Article
- Cathepsin L in Lung Adenocarcinoma: Prognostic Significance and Immunotherapy Response Through a Multi Omics Perspective.Cancer informatics · 2024Article
- The Potential of Extracellular Matrix- and Integrin Adhesion Complex-Related Molecules for Prostate Cancer Biomarker Discovery.Biomedicines · 2023Review
- Methyltransferase-like 3 promotes cervical cancer metastasis by enhancing cathepsin L mRNA stability in an N6-methyladenosine-dependent manner.Cancer science · 2023Article
- The Spatial Landscape of Progression and Immunoediting in Primary Melanoma at Single-Cell Resolution.Cancer discovery · 2022Article
- Helicobacter pylori and gastric cancer: a lysosomal protease perspective.Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association · 2022Review
- Effects of high-intensity training on prostate cancer-induced cardiac atrophy.American journal of translational research · 2021Article
- Identification and Validation of a Tumor Microenvironment-Related Gene Signature for Prognostic Prediction in Advanced-Stage Non-Small-Cell Lung Cancer.BioMed research international · 2021Article
- Cathepsin L interacts with CDK2-AP1 as a potential predictor of prognosis in patients with breast cancer.Oncology letters · 2020Article
- Article
- 'Patchiness' and basic cancer research: unravelling the proteases.Cell cycle (Georgetown, Tex.) · 2019Review
- Cathepsin L activated by mutant p53 and Egr-1 promotes ionizing radiation-induced EMT in human NSCLC.Journal of experimental & clinical cancer research : CR · 2019Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
It is estimated that approximately 90% of patients with advanced prostate cancer develop bone metastases; an occurrence that results in a substantial reduction in the quality of life and a drastic worsening of prognosis. The development of novel therapeutic strategies that impair the metastatic process and associated skeletal adversities is therefore critical to improving prostate cancer patient survival. Recognition of the importance of Cathepsin L (CTSL) to metastatic dissemination of cancer cells has led to the development of several CTSL inhibition strategies. The present investigation employed intra-cardiac injection of human PC-3ML prostate cancer cells into nude mice to examine tumor cell dissemination in a preclinical bone metastasis model. CTSL knockdown confirmed the validity of targeting this protease and subsequent intervention studies with the small molecule CTSL inhibitor KGP94 resulted in a significant reduction in metastatic tumor burden in the bone and an improvement in overall survival. CTSL inhibition by KGP94 also led to a significant impairment of tumor initiated angiogenesis. Furthermore, KGP94 treatment decreased osteoclast formation and bone resorptive function, thus, perturbing the reciprocal interactions between tumor cells and osteoclasts within the bone microenvironment which typically result in bone loss and aggressive growth of metastases. These functional effects were accompanied by a significant downregulation of NFκB signaling activity and expression of osteoclastogenesis related NFκB target genes. Collectively, these data indicate that the CTSL inhibitor KGP94 has the potential to alleviate metastatic disease progression and associated skeletal morbidities and hence may have utility in the treatment of advanced prostate cancer patients.
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Registered trials
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