ArticleCancer cell2020
Altered RNA Splicing by Mutant p53 Activates Oncogenic RAS Signaling in Pancreatic Cancer.
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Article in Cancer cell, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 116 papers.
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116citing papers in PubMed
8.3field-weighted citation impact, top 1% of its field
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Who cites it
116 citing papers in PubMed, 155 citations in OpenAlex.
- Radical Antegrade Modular Pancreatosplenectomy Versus Standard Resection in T3 Body and Tail Pancreatic Ductal Adenocarcinoma: A Multicenter Retrospective Cohort Study.Annals of surgical oncology · 2026Article
- MYC-Mediated USP39 Upregulation Stabilizes SRSF1 in Pancreatic Cancer.Molecular cancer research : MCR · 2026Article
- Deconvoluting the multi-faceted roles of alternative splicing events in cancer: From underlying mechanisms to innovative therapeutics.Acta pharmaceutica Sinica. B · 2026Review
- Twist1 overexpression models an aggressive subtype of pancreatic ductal adenocarcinoma in vivo.Lab animal · 2026Article
- U2 snRNP inhibition hampers pancreatic cancer cell viability by disrupting DNA repair proficiency and mitotic checkpoint integrity.Journal of experimental & clinical cancer research : CR · 2026Article
- The splice of life: an isoform-centric view of disease, technology, and therapeutics.The Journal of clinical investigation · 2026Review
- Improving pancreatic adenocarcinoma prognosis models through ligand receptor interactions and histopathological integration.Journal of translational medicine · 2026Article
- Uncovering molecular pathways in appendiceal cancer: A comprehensive characterization for precision oncology.American journal of surgery · 2026Article
- Peptides as integrative modulators for clinical prognosis and targeted therapy in pancreatic cancer.Discover oncology · 2026Review
- Dynamic ecosystems of tumor drug resistance mechanisms: from molecular heterogeneity to systemic interventions.Apoptosis : an international journal on programmed cell death · 2026Review
- UBA6 serves as a prognostic biomarker and promotes tumor progression in pancreatic ductal adenocarcinoma.Translational cancer research · 2026Article
- Dual Targeting of Mutant p53 and SNRPD2 via Engineered Exosomes Modulates Alternative Splicing to Suppress Ovarian Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Mutant p53 promotes clonal hematopoiesis by generating a chronic inflammatory microenvironment.The Journal of clinical investigation · 2026Article
- Opportunities for RNA sequencing in physiology: from big data to understanding homeostasis and heterogeneity.Function (Oxford, England) · 2026Review
- IFN-γ-driven UBE2D3 upregulation impairs antigen presentation pathways and anti-tumor immunity in pancreatic cancer.Nature communications · 2025Article
- Expression of IMPACT Curtails Metabolic Plasticity and Augments NK Cell Killing to Abrogate Metastatic Growth.Cancer discovery · 2025Article
- Impact of TP53, KRAS, and APC Mutations on Neoadjuvant Chemotherapy Outcomes in Locally Advanced Rectal Cancer.Cancer science · 2025Article
- Bioinformatics frameworks for single-cell long-read sequencing: unlocking isoform-level resolution.Briefings in bioinformatics · 2025Review
- Coexistence of P53 and KRAS mutations enhances ERK1/2 signaling by inducing EGR1 expression through mutp53 and c-JUN interaction.Oncogene · 2025Article
- Real-world evidence of chemotherapy effects in advanced pancreatic ductal adenocarcinoma: prognostic significance ofESMO gastrointestinal oncology · 2025Article
56 more citing papers are in PubMed but not listed here.
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Authors and funding
44 authors at 14 institutions in 5 countries.
Luisa F Escobar-HoyosDavid M. Rubenstein Center for Pancreatic Cancer Research, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Department of Therapeutic Radiology, Yale University, School of Medicine, New Haven, CT 06520, USA; Department of Biology, Research Group Genetic Toxicology and Cytogenetics, School of Natural Sciences and Education, Universidad del Cauca, Popayán, Colombia; Department of Pathology, Renaissance School of Medicine, Stony Brook University, New York, NY 11794, USA. Electronic address: luisa.escobar-hoyos@yale.edu.
Alex PensonHuman Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Marie-José and Henry R. Kravis Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Ram KannanHoward Hughes Medical Institute, Cancer Biology & Genetics Program, Sloan-Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Hana ChoHuman Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Chun-Hao PanDepartment of Pathology, Renaissance School of Medicine, Stony Brook University, New York, NY 11794, USA.
Rohit K SinghInstitute of Biochemistry, University of Münster, Münster, Germany.
Lisa H ApkenInstitute of Molecular Tumor Biology, University of Münster, Münster, Germany.
G Aaron HobbsLineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Renhe LuoGerstner Sloan Kettering Graduate School of Biomedical Sciences, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Nicolas LecomteDavid M. Rubenstein Center for Pancreatic Cancer Research, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Sruthi BabuDepartment of Pathology, Renaissance School of Medicine, Stony Brook University, New York, NY 11794, USA.
Fong Cheng PanDavid M. Rubenstein Center for Pancreatic Cancer Research, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Direna Alonso-CurbeloDavid M. Rubenstein Center for Pancreatic Cancer Research, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Marie-José and Henry R. Kravis Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
John P MorrisDavid M. Rubenstein Center for Pancreatic Cancer Research, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Marie-José and Henry R. Kravis Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Gokce AskanDavid M. Rubenstein Center for Pancreatic Cancer Research, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Olivera Grbovic-HuezoDavid M. Rubenstein Center for Pancreatic Cancer Research, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Marie-José and Henry R. Kravis Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Paul OgrodowskiHoward Hughes Medical Institute, Cancer Biology & Genetics Program, Sloan-Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Jonathan BermeoDavid M. Rubenstein Center for Pancreatic Cancer Research, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Joseph SaglimbeniDavid M. Rubenstein Center for Pancreatic Cancer Research, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Cristian D CruzDavid M. Rubenstein Center for Pancreatic Cancer Research, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Yu-Jui HoHoward Hughes Medical Institute, Cancer Biology & Genetics Program, Sloan-Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Sharon A LawrenceDavid M. Rubenstein Center for Pancreatic Cancer Research, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Jerry P MelchorDavid M. Rubenstein Center for Pancreatic Cancer Research, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Grant A GodaDepartment of Pharmacology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Department of Chemistry, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Karen BaiDepartment of Pathology, Renaissance School of Medicine, Stony Brook University, New York, NY 11794, USA.
Alessandro PastoreHuman Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Simon J HoggHuman Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Srivatsan RaghavanDepartment of Medical Oncology, Dana Farber Cancer Institute, Boston, MA 02215, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Peter BaileyDepartment of General Surgery, University of Heidelberg, Im Neuenheimer Feld 110, Heidelberg, Baden-Württemberg 69120, Germany; Institute of Cancer Sciences, University of Glasgow, Garscube Estate, Switchback Road, Bearsden, G61 1Q, Glasgow, UK.
David K ChangThe Kinghorn Cancer Centre, and the Cancer Research Program, Garvan Institute of Medical Research, Darlinghurst, Sydney, NSW, Australia; Department of Surgery, Bankstown Hospital, Eldridge Road, Bankstown, Sydney, NSW, Australia; South Western Sydney Clinical School, Faculty of Medicine, University of New South Wales, Liverpool, NSW, Australia.
Andrew BiankinDepartment of General Surgery, University of Heidelberg, Im Neuenheimer Feld 110, Heidelberg, Baden-Württemberg 69120, Germany; Institute of Cancer Sciences, University of Glasgow, Garscube Estate, Switchback Road, Bearsden, G61 1Q, Glasgow, UK; The Kinghorn Cancer Centre, and the Cancer Research Program, Garvan Institute of Medical Research, Darlinghurst, Sydney, NSW, Australia; Department of Surgery, Bankstown Hospital, Eldridge Road, Bankstown, Sydney, NSW, Australia.
Kenneth R ShroyerDepartment of Pathology, Renaissance School of Medicine, Stony Brook University, New York, NY 11794, USA.
Brian M WolpinDepartment of Medical Oncology, Dana Farber Cancer Institute, Boston, MA 02215, USA.
Andrew J AguirreDepartment of Medical Oncology, Dana Farber Cancer Institute, Boston, MA 02215, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Andrea VenturaHoward Hughes Medical Institute, Cancer Biology & Genetics Program, Sloan-Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Barry TaylorHuman Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Marie-José and Henry R. Kravis Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Departments of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Channing J DerLineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; Department of Pharmacology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Daniel DominguezLineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; Department of Pharmacology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Daniel KümmelInstitute of Biochemistry, University of Münster, Münster, Germany.
Andrea OeckinghausInstitute of Molecular Tumor Biology, University of Münster, Münster, Germany.
Scott W LoweDavid M. Rubenstein Center for Pancreatic Cancer Research, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Howard Hughes Medical Institute, Cancer Biology & Genetics Program, Sloan-Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA.
Robert K BradleyFred Hutchinson Cancer Research Center Seattle, Seattle, WA 98109-1024, USA.
Omar Abdel-WahabHuman Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Steven D LeachDavid M. Rubenstein Center for Pancreatic Cancer Research, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Dartmouth Norris Cotton Cancer Center, Lebanon, NH 03766, USA. Electronic address: steven.d.leach@dartmouth.edu.
Memorial Sloan Kettering Cancer Center · USHoward Hughes Medical Institute · USUniversity of Münster · DEUniversity of North Carolina at Chapel Hill · USMolecular Oncology (United States) · USBroad Institute · USStony Brook School · USStony Brook University · USDana-Farber Cancer Institute · USDartmouth College · USFred Hutch Cancer Center · USGarvan Institute of Medical Research · AUUniversity of Glasgow · GBUNSW Sydney · AU
Funding
X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Nicholas D Socci · 1985 to 2026
$347.4MVIRAL TRANSACTIVATIONP01CA013106 · NCI · COLD SPRING HARBOR LABORATORY · PI William Richard McCombie · 1985 to 2026
$116.8MTranslational Engineering in Cancer (TEC)P30CA023108 · NCI · DARTMOUTH COLLEGE · PI Steven D Leach · 1985 to 2026
$91.3MScientific ReagentsP01CA087497 · NCI · COLUMBIA UNIV NEW YORK MORNINGSIDE · PI PRIVES, CAROL · 2000 to 2021
$35.4MPre-doctoral Training Program in Integrative Vascular BiologyT32HL069768 · NHLBI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Christopher P. Mack · 2002 to 2026
$9.7MGenetic and molecular basis for SRSF2 mutations in myelodysplasiaR01HL128239 · NHLBI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI Omar Abdel-Wahab, Robert K Bradley · 2015 to 2026
$8.0MTargeting undruggable RAS for cancer treatmentR35CA232113 · NCI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI DER, CHANNING J. · 2018 to 2024
$6.3MComprehensive genetic dissection of druggable KRAS targetsR01CA204228 · NCI · SLOAN-KETTERING INST CAN RESEARCH · PI LEACH, STEVEN D · 2016 to 2020
$1.9MFunctional interrogation of epigenetic vulnerabilities in KRAS-mutant pancreatic cancerK08CA218420 · NCI · DANA-FARBER CANCER INST · PI AGUIRRE, ANDREW JAMES · 2017 to 2021
$886kAltered mRNA splicing dependent on mutant p53 identifies novel therapeutic vulnerability in pancreatic cancerR00CA226342 · NCI · YALE UNIVERSITY · PI ESCOBAR HOYOS, LUISA · 2020 to 2022
$741kAltered mRNA splicing dependent on mutant p53 identifies novel therapeutic vulnerability in pancreatic cancerK99CA226342 · NCI · SLOAN-KETTERING INST CAN RESEARCH · PI ESCOBAR HOYOS, LUISA · 2018 to 2019
$204kNCI NIH HHS K08 CA218420NCI NIH HHS K99 CA226342NCI NIH HHS P01 CA013106NCI NIH HHS P01 CA087497NCI NIH HHS P30 CA008748NCI NIH HHS P30 CA023108NCI NIH HHS R00 CA226342NCI NIH HHS R01 CA204228NCI NIH HHS R35 CA232113NHLBI NIH HHS R01 HL128239NHLBI NIH HHS T32 HL069768
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is driven by co-existing mutations in KRAS and TP53. However, how these mutations collaborate to promote this cancer is unknown. Here, we uncover sequence-specific changes in RNA splicing enforced by mutant p53 which enhance KRAS activity. Mutant p53 increases expression of splicing regulator hnRNPK to promote inclusion of cytosine-rich exons within GTPase-activating proteins (GAPs), negative regulators of RAS family members. Mutant p53-enforced GAP isoforms lose cell membrane association, leading to heightened KRAS activity. Preventing cytosine-rich exon inclusion in mutant KRAS/p53 PDACs decreases tumor growth. Moreover, mutant p53 PDACs are sensitized to inhibition of splicing via spliceosome inhibitors. These data provide insight into co-enrichment of KRAS and p53 mutations and therapeutics targeting this mechanism in PDAC.
Indexed as
MutationRNA SplicingAnimalsCarcinoma, Pancreatic DuctalCell Line, TumorCells, CulturedFemaleGene Expression Regulation, NeoplasticHumansKaplan-Meier EstimateMice, Inbred C57BLMice, KnockoutPancreatic NeoplasmsProto-Oncogene Proteins p21(ras)RNAi TherapeuticsSignal TransductionKRAS protein, humanProto-Oncogene Proteins p21(ras)TP53 protein, humanTumor Suppressor Protein p53GAP17GTPase signalinghnRNPKKRASoncogenesp53pancreatic cancerRNA splicingSF3B1splicing inhibitors
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