ArticleProceedings of the National Academy of Sciences of the United States of America2010
RBBP9: a tumor-associated serine hydrolase activity required for pancreatic neoplasia.
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 34 papers.
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Who cites it
34 citing papers in PubMed, 74 citations in OpenAlex.
- The metastatic cascade through the lens of therapeutic inhibition.Cell reports. Medicine · 2025Review
- KLK7, KLK10, and KLK11 in Papillary Thyroid Cancer: Bioinformatic Analysis and Experimental Validation.Biochemical genetics · 2024Article
- Genome-wide siRNA screens identify RBBP9 function as a potential target in Fanconi anaemia-deficient head-and-neck squamous cell carcinoma.Communications biology · 2023Article
- Genes associated with diagnosis and prognosis of Burkitt lymphoma.IET systems biology · 2022Article
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- Integrative network analysis revealed the molecular function of folic acid on immunological enhancement in a sheep model.Frontiers in immunology · 2022Article
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- Application of the RBBP9 Serine Hydrolase Inhibitor, ML114, Decouples Human Pluripotent Stem Cell Proliferation and Differentiation.International journal of molecular sciences · 2020Article
- Tailored therapeutics based on 1,2,3-1MedChemComm · 2019Review
- Late-Stage Conversion of Diphenylphosphonate to Fluorophosphonate Probes for the Investigation of Serine Hydrolases.Cell chemical biology · 2019Article
- PEG-b-poly (carbonate)-derived nanocarrier platform with pH-responsive properties for pancreatic cancer combination therapy.Colloids and surfaces. B, Biointerfaces · 2019Article
- Proteome-Wide Structural Biology: An Emerging Field for the Structural Analysis of Proteins on the Proteomic Scale.Journal of proteome research · 2018Review
- APT2 Inhibition Restores Scribble Localization and S-Palmitoylation in Snail-Transformed Cells.Cell chemical biology · 2017Article
- A novel 3D mesenchymal stem cell model of the multiple myeloma bone marrow niche: biologic and clinical applications.Oncotarget · 2016Article
- Carboxylesterase 2 as a Determinant of Response to Irinotecan and Neoadjuvant FOLFIRINOX Therapy in Pancreatic Ductal Adenocarcinoma.Journal of the National Cancer Institute · 2015Article
- Exploring metabolic pathways and regulation through functional chemoproteomic and metabolomic platforms.Chemistry & biology · 2014Review
- Activity-based proteomic and metabolomic approaches for understanding metabolism.Current opinion in biotechnology · 2014Review
- A high-throughput, multiplexed assay for superfamily-wide profiling of enzyme activity.Nature chemical biology · 2014Article
- Article
- Chemical approaches to study metabolic networks.Pflugers Archiv : European journal of physiology · 2013Review
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12 authors at 3 institutions in 1 country.
Funding
Abstract
Pancreatic cancer is one of the most lethal malignancies. To discover functionally relevant modulators of pancreatic neoplasia, we performed activity-based proteomic profiling on primary human ductal adenocarcinomas. Here, we identify retinoblastoma-binding protein 9 (RBBP9) as a tumor-associated serine hydrolase that displays elevated activity in pancreatic carcinomas. Whereas RBBP9 is expressed in normal and malignant tissues at similar levels, its elevated activity in tumor cells promotes anchorage-independent growth in vitro as well as pancreatic carcinogenesis in vivo. At the molecular level, RBBP9 activity overcomes TGF-beta-mediated antiproliferative signaling by reducing Smad2/3 phosphorylation, a previously unknown role for a serine hydrolase in cancer biology. Conversely, loss of endogenous RBBP9 or expression of mutationally inactive RBBP9 leads to elevated Smad2/3 phosphorylation, implicating this serine hydrolase as an essential suppressor of TGF-beta signaling. Finally, RBBP9-mediated suppression of TGF-beta signaling is required for E-cadherin expression as loss of the serine hydrolase activity leads to a reduction in E-cadherin levels and a concomitant decrease in the integrity of tumor cell-cell junctions. These data not only define a previously uncharacterized serine hydrolase activity associated with epithelial neoplasia, but also demonstrate the potential benefit of functional proteomics in the identification of new therapeutic targets.
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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.