ArticleOncotarget2015
Nuclear cathepsin D enhances TRPS1 transcriptional repressor function to regulate cell cycle progression and transformation in human breast cancer cells.
Article in Oncotarget, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 42 citations in OpenAlex.
- Identification of an efficient immunohistochemical panel for precise differential diagnosis of sebaceous carcinoma of eyelid.Discover oncology · 2025Article
- Cathepsin D promotes acute myeloid leukemia progression through stabilization of the anti-apoptotic proteins.Cell death & disease · 2025Article
- Review
- Investigating the role of cathepsins in breast cancer progression: a Mendelian randomization study.Frontiers in oncology · 2025Article
- Cathepsin V regulates cell cycle progression and histone stability in the nucleus of breast cancer cells.Frontiers in pharmacology · 2023Article
- Low-level lysosomal membrane permeabilization for limited release and sublethal functions of cathepsin proteases in the cytosol and nucleus.FEBS open bio · 2022Review
- Cathepsin D as a potential therapeutic target to enhance anticancer drug-induced apoptosis via RNF183-mediated destabilization of Bcl-xL in cancer cells.Cell death & disease · 2022Article
- The noncanonical role of the protease cathepsin D as a cofilin phosphatase.Cell research · 2021Article
- The Role of Cysteine Peptidases in Hematopoietic Stem Cell Differentiation and Modulation of Immune System Function.Frontiers in immunology · 2021Review
- A 9-kDa matricellular SPARC fragment released by cathepsin D exhibits pro-tumor activity in the triple-negative breast cancer microenvironment.Theranostics · 2021Article
- Unravelling the Network of Nuclear Matrix Metalloproteinases for Targeted Drug Design.Biology · 2020Review
- Late endosomes promote microglia migration via cytosolic translocation of immature protease cathD.Science advances · 2020Article
- Integrative p53, micro-RNA and Cathepsin Protease Co-Regulatory Expression Networks in Cancer.Cancers · 2020Review
- Clinical significance and biological function of transcriptional repressor GATA binding 1 in gastric cancer: a study based on data mining, RT-qPCR, immunochemistry, and vitro experiment.Cell cycle (Georgetown, Tex.) · 2020Article
- Cathepsin D deficiency in mammary epithelium transiently stalls breast cancer by interference with mTORC1 signaling.Nature communications · 2020Article
- Lysosomal Hydrolase Cathepsin D Non-proteolytically Modulates Dendritic Morphology in Drosophila.Neuroscience bulletin · 2020Article
- Review
- Cysteine Cathepsin Protease Inhibition: An update on its Diagnostic, Prognostic and Therapeutic Potential in Cancer.Pharmaceuticals (Basel, Switzerland) · 2019Review
- Lysosomal cathepsin D is upregulated in Alzheimer's disease neocortex and may be a marker for neurofibrillary degeneration.Brain pathology (Zurich, Switzerland) · 2019Article
- TRPS1 Suppresses Breast Cancer Epithelial-mesenchymal Transition Program as a Negative Regulator of SUZ12.Translational oncology · 2018Article
Corrections and comments
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Authors and funding
17 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The lysosomal protease cathepsin D (Cath-D) is overproduced in breast cancer cells (BCC) and supports tumor growth and metastasis formation. Here, we describe the mechanism whereby Cath-D is accumulated in the nucleus of ERα-positive (ER+) BCC. We identified TRPS1 (tricho-rhino-phalangeal-syndrome 1), a repressor of GATA-mediated transcription, and BAT3 (Scythe/BAG6), a nucleo-cytoplasmic shuttling chaperone protein, as new Cath-D-interacting nuclear proteins. Cath-D binds to BAT3 in ER+ BCC and they partially co-localize at the surface of lysosomes and in the nucleus. BAT3 silencing inhibits Cath-D accumulation in the nucleus, indicating that Cath-D nuclear targeting is controlled by BAT3. Fully mature Cath-D also binds to full-length TRPS1 and they co-localize in the nucleus of ER+ BCC where they are associated with chromatin. Using the LexA-VP16 fusion co-activator reporter assay, we then show that Cath-D acts as a transcriptional repressor, independently of its catalytic activity. Moreover, microarray analysis of BCC in which Cath-D and/or TRPS1 expression were silenced indicated that Cath-D enhances TRPS1-mediated repression of several TRPS1-regulated genes implicated in carcinogenesis, including PTHrP, a canonical TRPS1 gene target. In addition, co-silencing of TRPS1 and Cath-D in BCC affects the transcription of cell cycle, proliferation and transformation genes, and impairs cell cycle progression and soft agar colony formation. These findings indicate that Cath-D acts as a nuclear transcriptional cofactor of TRPS1 to regulate ER+ BCC proliferation and transformation in a non-proteolytic manner.
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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.