ArticleClinical & experimental metastasis2016
Cathepsin L in tumor angiogenesis and its therapeutic intervention by the small molecule inhibitor KGP94.
Article in Clinical & experimental metastasis, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 49 citations in OpenAlex.
- Cathepsin L as a Driver of Tumour Invasion and a Novel Therapeutic Target in Ovarian Cancer.Cancers · 2026Review
- Targeted approach to determine the impact of cancer-associated protease variants.Science advances · 2025Article
- Macrophage-derived cathepsin L promotes epithelial-mesenchymal transition and M2 polarization in gastric cancer.World journal of gastroenterology · 2024Article
- Cysteine protease I29 propeptide from Calotropis procera R. Br. As a potent cathepsin L inhibitor and its suppressive activity in breast cancer metastasis.Scientific reports · 2024Article
- A novel approach for transforming breast cancer stem cells into endothelial cells.Experimental and therapeutic medicine · 2024Article
- CTSL, a prognostic marker of breast cancer, that promotes proliferation, migration, and invasion in cells in triple-negative breast cancer.Frontiers in oncology · 2023Article
- Characterization and molecular docking study of cathepsin L inhibitory peptides (SnuCalCpIs) from Calotropis procera R. Br.Scientific reports · 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
- Expressions and significances of CTSL, the target of COVID-19 on GBM.Journal of cancer research and clinical oncology · 2022Article
- The mechanistic immunosuppressive role of the tumour vasculature and potential nanoparticle-mediated therapeutic strategies.Frontiers in immunology · 2022Review
- Bioprinting on Live Tissue for Investigating Cancer Cell Dynamics.Tissue engineering. Part A · 2021Article
- Vitamin D in Triple-Negative and BRCA1-Deficient Breast Cancer-Implications for Pathogenesis and Therapy.International journal of molecular sciences · 2020Review
- Cysteine Cathepsins Inhibition Affects Their Expression and Human Renal Cancer Cell Phenotype.Cancers · 2020Article
- A Review of Small Molecule Inhibitors and Functional Probes of Human Cathepsin L.Molecules (Basel, Switzerland) · 2020Review
- 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
- Axl signaling is an important mediator of tumor angiogenesis.Oncotarget · 2019Article
- Graphene Oxide-Based Targeting of Extracellular Cathepsin D and Cathepsin L As A Novel Anti-Metastatic Enzyme Cancer Therapy.Cancers · 2019Article
- Copy number profiling of Oncotype DX genes reveals association with survival of breast cancer patients.Molecular biology reports · 2018Article
Corrections and comments
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Authors and funding
4 authors at 3 institutions in 2 countries.
Funding
Abstract
A significant proportion of breast cancer patients harbor clinically undetectable micrometastases at the time of diagnosis. If left untreated, these micro-metastases may lead to disease relapse and possibly death. Hence, there is significant interest in the development of novel anti-metastatic agents that could also curb the growth of pre-established micrometastases. Like primary tumor, the growth of metastases also is driven by angiogenesis. Although the role of cysteine protease Cathepsin L (CTSL) in metastasis associated tumor cell functions such as migration and invasion is well recognized, its role in tumor angiogenesis remains less explored. The present study examines the contribution of CTSL to breast cancer angiogenesis and evaluates the anti-angiogenic efficacy of CTSL inhibitor KGP94. CTSL semi-quantitative RT-PCR analysis on breast tissue panels revealed significant upregulation of CTSL in breast cancer patients which strongly correlated with increased relapse and metastatic incidence and poor overall survival. Preclinically, CTSL ablation using shRNA or KGP94 treatment led to a significant reduction in MDA-MB-231 tumor cell induced angiogenesis in vivo. In-vitro assessments demonstrated a significant decrease in various angiogenic properties such as endothelial cell sprouting, migration, invasion, tube formation and proliferation in the presence of KGP94. Microarray analyses revealed a significant upregulation of cell cycle related genes by CTSL. Western blot analyses further confirmed upregulation of members of the cyclin family by CTSL. Collectively, these data indicate that CTSL is an important contributor to tumor angiogenesis and that the CTSL inhibition may have therapeutic utility in the treatment of breast cancer patients.
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