Nature Communications (Apr 2022)
USP25 promotes pathological HIF-1-driven metabolic reprogramming and is a potential therapeutic target in pancreatic cancer
- Jessica K. Nelson,
- May Zaw Thin,
- Theodore Evan,
- Steven Howell,
- Mary Wu,
- Bruna Almeida,
- Nathalie Legrave,
- Duco S. Koenis,
- Gabriela Koifman,
- Yoichiro Sugimoto,
- Miriam Llorian Sopena,
- James MacRae,
- Emma Nye,
- Michael Howell,
- Ambrosius P. Snijders,
- Andreas Prachalias,
- Yoh Zen,
- Debashis Sarker,
- Axel Behrens
Affiliations
- Jessica K. Nelson
- Adult Stem Cell Laboratory, The Francis Crick Institute
- May Zaw Thin
- Adult Stem Cell Laboratory, The Francis Crick Institute
- Theodore Evan
- Adult Stem Cell Laboratory, The Francis Crick Institute
- Steven Howell
- Proteomics, The Francis Crick Institute
- Mary Wu
- High Throughput Screening, The Francis Crick Institute
- Bruna Almeida
- Experimental Histopathology, The Francis Crick Institute
- Nathalie Legrave
- Metabolomics, The Francis Crick Institute
- Duco S. Koenis
- William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, Charterhouse Square
- Gabriela Koifman
- Adult Stem Cell Laboratory, The Francis Crick Institute
- Yoichiro Sugimoto
- Hypoxia Biology Laboratory, The Francis Crick Institute
- Miriam Llorian Sopena
- Bioinformatics and Biostatistics, The Francis Crick Institute
- James MacRae
- Metabolomics, The Francis Crick Institute
- Emma Nye
- Experimental Histopathology, The Francis Crick Institute
- Michael Howell
- High Throughput Screening, The Francis Crick Institute
- Ambrosius P. Snijders
- Proteomics, The Francis Crick Institute
- Andreas Prachalias
- Hepatobiliary and Pancreatic Surgery, King’s College Hospital, Denmark Hill
- Yoh Zen
- Institute of Liver Studies, King’s College Hospital, Denmark Hill
- Debashis Sarker
- School of Cancer and Pharmaceutical Sciences, King’s College Hospital, Denmark Hill
- Axel Behrens
- Adult Stem Cell Laboratory, The Francis Crick Institute
- DOI
- https://doi.org/10.1038/s41467-022-29684-9
- Journal volume & issue
-
Vol. 13,
no. 1
pp. 1 – 18
Abstract
The biological roles of deubiquitinating enzymes (DUBs) in pancreatic ductal adenocarcinoma (PDAC) are not fully explored. Here the authors perform activity based proteomics with a loss of function genetic screen and identify that USP25 promotes PDAC growth and survival through HIF-1 protein stability and transcriptional activity.