ArticleGenes & development2021
USP21 deubiquitinase elevates macropinocytosis to enable oncogenic KRAS bypass in pancreatic cancer.
Article in Genes & development, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
What it found
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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
22 citing papers in PubMed, 31 citations in OpenAlex.
- Overcoming Adaptive Resistance to KRASG12D Blockade in Pancreatic Cancer through Vertical Pathway Inhibition.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026Article
- USP21 functions as an oncogenic regulator of the Mdm2-p53 axis in colorectal cancer.Cell death discovery · 2026Article
- Aldolase a coordinates macropinocytic nutrient scavenging and lysosomal degradation in lung cancer by interacting with V-ATPase.Cell communication and signaling : CCS · 2025Article
- The tumour microenvironment in pancreatic cancer - new clinical challenges, but more opportunities.Nature reviews. Clinical oncology · 2025Review
- The multifaceted roles of deubiquitinating enzymes (DUBs) in pancreatic ductal adenocarcinoma.Cell death & disease · 2025Review
- Novel paradigms in KRAS targeting: Unveiling strategies to combat drug resistance.Chinese medical journal · 2025Review
- Targeting USP21 to inhibit abdominal aortic aneurysm progression by suppressing the phenotypic transition of vascular smooth muscle cells.Cell reports. Medicine · 2025Article
- Genetics and biology of pancreatic ductal adenocarcinoma.Genes & development · 2025Review
- Mechanisms of Resistance to Oncogenic KRAS Inhibition in Pancreatic Cancer.Cancer discovery · 2024Article
- Ubiquitin-specific protease 21 promotes tumorigenicity and stemness of colorectal cancer by deubiquitinating and stabilizing ZEB1.World journal of gastrointestinal oncology · 2024Article
- A Small Molecule with Big Impact: MRTX1133 Targets the KRASG12D Mutation in Pancreatic Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024Article
- The ubiquitin-proteasome system in the tumor immune microenvironment: a key force in combination therapy.Frontiers in immunology · 2024Review
- Honokiol enhances the sensitivity of cetuximab in KRASTheranostics · 2024Article
- KRAS-Dependency in Pancreatic Ductal Adenocarcinoma: Mechanisms of Escaping in Resistance to KRAS Inhibitors and Perspectives of Therapy.International journal of molecular sciences · 2023Review
- KRAS Mutations in Solid Tumors: Characteristics, Current Therapeutic Strategy, and Potential Treatment Exploration.Journal of clinical medicine · 2023Review
- Ubiquitin signaling in pancreatic ductal adenocarcinoma.Frontiers in molecular biosciences · 2023Review
- RHBDL2 promotes the proliferation, migration, and invasion of pancreatic cancer by stabilizing the N1ICD via the OTUD7B and activating the Notch signaling pathway.Cell death & disease · 2022Article
- Loss of Heterozygosity forInternational journal of molecular sciences · 2022Article
- Conquering oncogenic KRAS and its bypass mechanisms.Theranostics · 2022Review
- The Role and Therapeutic Potential of Macropinocytosis in Cancer.Frontiers in pharmacology · 2022Review
Corrections and comments
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Authors and funding
17 authors at 3 institutions in 2 countries.
Funding
Abstract
Activating mutations in KRAS (KRAS*) are present in nearly all pancreatic ductal adenocarcinoma (PDAC) cases and critical for tumor maintenance. By using an inducible KRAS* PDAC mouse model, we identified a deubiquitinase USP21-driven resistance mechanism to anti-KRAS* therapy. USP21 promotes KRAS*-independent tumor growth via its regulation of MARK3-induced macropinocytosis, which serves to maintain intracellular amino acid levels for anabolic growth. The USP21-mediated KRAS* bypass, coupled with the frequent amplification of USP21 in human PDAC tumors, encourages the assessment of USP21 as a novel drug target as well as a potential parameter that may affect responsiveness to emergent anti-KRAS* therapy.
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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.