ArticleJournal of cell science2010
Pro-cathepsin D interacts with the extracellular domain of the beta chain of LRP1 and promotes LRP1-dependent fibroblast outgrowth.
Article in Journal of cell science, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
What it found
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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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
33 citing papers in PubMed, 63 citations in OpenAlex.
- Lipid metabolic reprograming: the unsung hero in breast cancer progression and tumor microenvironment.Molecular cancer · 2025Review
- Antibodies against the multifaceted cathepsin D protein open new avenues for TNBC immunotherapy.Journal for immunotherapy of cancer · 2025Article
- Novel insights into the multifaceted and tissue-specific roles of the endocytic receptor LRP1.The Journal of biological chemistry · 2024Review
- A novel Fc-engineered cathepsin D-targeting antibody enhances ADCC, triggers tumor-infiltrating NK cell recruitment, and improves treatment with paclitaxel and enzalutamide in triple-negative breast cancer.Journal for immunotherapy of cancer · 2024Article
- Reprogramming of Lipid Metabolism Mediates Crosstalk, Remodeling, and Intervention of Microenvironment Components in Breast Cancer.International journal of biological sciences · 2024Review
- Construction of cancer- associated fibroblasts related risk signature based on single-cell RNA-seq and bulk RNA-seq data in bladder urothelial carcinoma.Frontiers in oncology · 2023Article
- Review
- A 9-kDa matricellular SPARC fragment released by cathepsin D exhibits pro-tumor activity in the triple-negative breast cancer microenvironment.Theranostics · 2021Article
- Coding transcriptome analyses reveal altered functions underlying immunotolerance of PEG-fused rat sciatic nerve allografts.Journal of neuroinflammation · 2020Article
- Article
- LRP-1 Promotes Colon Cancer Cell Proliferation in 3D Collagen Matrices by Mediating DDR1 Endocytosis.Frontiers in cell and developmental biology · 2020Article
- Immunotherapy of triple-negative breast cancer with cathepsin D-targeting antibodies.Journal for immunotherapy of cancer · 2019Article
- Naturally Occurring Variants in LRP1 (Low-Density Lipoprotein Receptor-Related Protein 1) Affect HDL (High-Density Lipoprotein) Metabolism Through ABCA1 (ATP-Binding Cassette A1) and SR-B1 (Scavenger Receptor Class B Type 1) in Humans.Arteriosclerosis, thrombosis, and vascular biology · 2018Article
- Quantitative Proteome Analysis of Mouse Liver Lysosomes Provides Evidence for Mannose 6-phosphate-independent Targeting Mechanisms of Acid Hydrolases in Mucolipidosis II.Molecular & cellular proteomics : MCP · 2017Article
- Subcellular Trafficking of Mammalian Lysosomal Proteins: An Extended View.International journal of molecular sciences · 2016Review
- Procathepsin E is highly abundant but minimally active in pancreatic ductal adenocarcinoma tumors.Biological chemistry · 2016Article
- Nuclear cathepsin D enhances TRPS1 transcriptional repressor function to regulate cell cycle progression and transformation in human breast cancer cells.Oncotarget · 2015Article
- The Matricellular Receptor LRP1 Forms an Interface for Signaling and Endocytosis in Modulation of the Extracellular Tumor Environment.Frontiers in pharmacology · 2015Review
- Two Faces of Cathepsin D: Physiological Guardian Angel and Pathological Demon.Biology and medicine (Aligarh) · 2014Article
- Article
Corrections and comments
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Authors and funding
16 authors at 10 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Interactions between cancer cells and fibroblasts are crucial in cancer progression. We have previously shown that the aspartic protease cathepsin D (cath-D), a marker of poor prognosis in breast cancer that is overexpressed and highly secreted by breast cancer cells, triggers mouse embryonic fibroblast outgrowth via a paracrine loop. Here, we show the requirement of secreted cath-D for human mammary fibroblast outgrowth using a three-dimensional co-culture assay with breast cancer cells that do or do not secrete pro-cath-D. Interestingly, proteolytically-inactive pro-cath-D remains mitogenic, indicating a mechanism involving protein-protein interaction. We identify the low-density lipoprotein (LDL) receptor-related protein-1, LRP1, as a novel binding partner for pro-cath-D in fibroblasts. Pro-cath-D binds to residues 349-394 of the β chain of LRP1, and is the first ligand of the extracellular domain of LRP1β to be identified. We show that pro-cath-D interacts with LRP1β in cellulo. Interaction occurs at the cell surface, and overexpressed LRP1β directs pro-cath-D to the lipid rafts. Our results reveal that the ability of secreted pro-cath-D to promote human mammary fibroblast outgrowth depends on LRP1 expression, suggesting that pro-cath-D-LRP1β interaction plays a functional role in the outgrowth of fibroblasts. Overall, our findings strongly suggest that pro-cath-D secreted by epithelial cancer cells promotes fibroblast outgrowth in a paracrine LRP1-dependent manner in the breast tumor microenvironment.
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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.