ArticleCancer cell2020
Unbiased Proteomic Profiling Uncovers a Targetable GNAS/PKA/PP2A Axis in Small Cell Lung Cancer Stem Cells.
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In one paragraph
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 58 papers, 1 of them a synthesis that pooled it.
0numbers the graph read from it
0cells of the map it votes in
58citing papers in PubMed, 1 pooled it
5.0field-weighted citation impact, top 4% of its field
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Who cites it
58 citing papers in PubMed, 1 synthesis or guideline pooled it, 85 citations in OpenAlex.
- A multiplexed in vivo approach to identify driver genes in small cell lung cancer.Cell reports · 2023Pooled it
- Mass Spectrometric Detected Cancer Proteins as Resources for Cancer Research.Journal of proteome research · 2026Article
- GNAS/PKA signaling promotes aberrant osteochondral differentiation of Gli1The EMBO journal · 2025Article
- The cAMP-PKA signaling initiates mitosis by phosphorylating Bora.Nature communications · 2025Article
- Protein kinase A is a dependent factor and therapeutic target in mouse models of fibrous dysplasia.Nature communications · 2025Article
- Molecular and functional profiling unravels targetable vulnerabilities in colorectal cancer.Molecular oncology · 2025Article
- Neuroendocrine neoplasms of the lung: The latest updates.World journal of clinical oncology · 2025Review
- The evolution of AKAPs and emergence of PKA isotype selective anchoring determinants.The Journal of biological chemistry · 2025Article
- Contract to kill: GNAS mutation.Molecular cancer · 2025Review
- Sympathetic Neurons Promote Small Cell Lung Cancer through the β2-Adrenergic Receptor.Cancer discovery · 2025Article
- The PDE4DIP-AKAP9 axis promotes lung cancer growth through modulation of PKA signalling.Communications biology · 2025Article
- KHSRP promotes cancer stem cell maintenance, tumorigenesis, and suppresses anti-tumor immunity in gastric cancer.Oncology research · 2025Article
- Protein kinase A and local signaling in cancer.The Biochemical journal · 2024Review
- GNAS knockout potentiates HDAC3 inhibition through viral mimicry-related interferon responses in lymphoma.Leukemia · 2024Article
- Small Cell Lung Cancer Neuronal Features and Their Implications for Tumor Progression, Metastasis, and Therapy.Molecular cancer research : MCR · 2024Review
- PRKDC Induces Chemoresistance in Osteosarcoma by Recruiting GDE2 to Stabilize GNAS and Activate AKT.Cancer research · 2024Article
- TIPRL Regulates Stemness and Survival in Lung Cancer Stem Cells through CaMKK2-CaMK4-CREB Feedback Loop Activation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Cordycepin Triphosphate as a Potential Modulator of Cellular Plasticity in Cancer via cAMP-Dependent Pathways: An In Silico Approach.International journal of molecular sciences · 2024Article
- DNA methylation landscape reveals GNAS as a decitabine-responsive marker in patients with acute myeloid leukemia.Neoplasia (New York, N.Y.) · 2024Article
- Association of elevated autoantibody to high expression of GNAS in hepatocellular carcinoma.Heliyon · 2023Article
Corrections and comments
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Authors and funding
28 authors at 9 institutions in 1 country.
Garry L ColesDepartment of Pediatrics, Stanford University, 265 Campus Drive, Stanford, CA 94305-5457, USA; Department of Genetics, Stanford University, Stanford, CA 94305, USA.
Sandra CristeaDepartment of Pediatrics, Stanford University, 265 Campus Drive, Stanford, CA 94305-5457, USA; Department of Genetics, Stanford University, Stanford, CA 94305, USA.
James T WebberDepartment of Bioengineering and Therapeutic Sciences, University of California San Francisco, San Francisco, CA 94158, USA.
Rebecca S LevinHoward Hughes Medical Institute, University of California San Francisco, San Francisco, CA 94158, USA; Department of Cellular and Molecular Pharmacology, University of California San Francisco, San Francisco, CA 94158, USA.
Steven M MossDepartment of Cellular and Molecular Pharmacology, University of California San Francisco, San Francisco, CA 94158, USA.
Andy HeDepartment of Pediatrics, Stanford University, 265 Campus Drive, Stanford, CA 94305-5457, USA; Department of Genetics, Stanford University, Stanford, CA 94305, USA.
Jaya SangodkarDivision of Genetic Medicine, Michigan Medicine, University of Michigan, Ann Arbor, MI, USA.
Yeonjoo C HwangDepartment of Medicine, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA 94143, USA.
Julia ArandDepartment of Pediatrics, Stanford University, 265 Campus Drive, Stanford, CA 94305-5457, USA; Department of Genetics, Stanford University, Stanford, CA 94305, USA.
Alexandros P DrainasDepartment of Pediatrics, Stanford University, 265 Campus Drive, Stanford, CA 94305-5457, USA; Department of Genetics, Stanford University, Stanford, CA 94305, USA.
Nancie A MooneyBaxter Laboratory, Stanford University, Stanford, CA 94305, USA; Department of Microbiology & Immunology, Stanford University, Stanford, CA 94305, USA.
Janos DemeterBaxter Laboratory, Stanford University, Stanford, CA 94305, USA; Department of Microbiology & Immunology, Stanford University, Stanford, CA 94305, USA.
Jessica N SpradlinDepartment of Chemistry, University of California, Berkeley, Berkeley, CA 94720, USA.
Brandon MauchDepartment of Pediatrics, Stanford University, 265 Campus Drive, Stanford, CA 94305-5457, USA; Department of Genetics, Stanford University, Stanford, CA 94305, USA.
Vicky LeDepartment of Pediatrics, Stanford University, 265 Campus Drive, Stanford, CA 94305-5457, USA; Department of Genetics, Stanford University, Stanford, CA 94305, USA.
Yan Ting ShueDepartment of Pediatrics, Stanford University, 265 Campus Drive, Stanford, CA 94305-5457, USA; Department of Genetics, Stanford University, Stanford, CA 94305, USA.
Julie H KoDepartment of Pediatrics, Stanford University, 265 Campus Drive, Stanford, CA 94305-5457, USA; Department of Genetics, Stanford University, Stanford, CA 94305, USA.
Myung Chang LeeDepartment of Pediatrics, Stanford University, 265 Campus Drive, Stanford, CA 94305-5457, USA; Department of Genetics, Stanford University, Stanford, CA 94305, USA.
Christina KongDepartment of Pathology, Stanford University, Stanford, CA 94305, USA.
Daniel K NomuraDepartment of Chemistry, University of California, Berkeley, Berkeley, CA 94720, USA; Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA; Department of Nutritional Sciences and Toxicology, University of California, Berkeley, Berkeley, CA 94720, USA.
Michael OhlmeyerIcahn School of Medicine at Mount Sinai, New York, NY, USA; Atux Iskay LLC, Plainsboro, New Jersey, NJ 08536, USA.
Danielle L SwaneyDepartment of Cellular and Molecular Pharmacology, University of California San Francisco, San Francisco, CA 94158, USA; Quantitative Biosciences Institute (QBI), University of California San Francisco, San Francisco, CA 94158, USA; David J. Gladstone Institute, University of California San Francisco, San Francisco, CA 94158, USA.
Nevan J KroganDepartment of Cellular and Molecular Pharmacology, University of California San Francisco, San Francisco, CA 94158, USA; Quantitative Biosciences Institute (QBI), University of California San Francisco, San Francisco, CA 94158, USA; David J. Gladstone Institute, University of California San Francisco, San Francisco, CA 94158, USA.
Peter K JacksonBaxter Laboratory, Stanford University, Stanford, CA 94305, USA; Department of Microbiology & Immunology, Stanford University, Stanford, CA 94305, USA; Department of Pathology, Stanford University, Stanford, CA 94305, USA.
Goutham NarlaDivision of Genetic Medicine, Michigan Medicine, University of Michigan, Ann Arbor, MI, USA.
John D GordanDepartment of Medicine, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA 94143, USA; Quantitative Biosciences Institute (QBI), University of California San Francisco, San Francisco, CA 94158, USA.
Kevan M ShokatHoward Hughes Medical Institute, University of California San Francisco, San Francisco, CA 94158, USA; Department of Cellular and Molecular Pharmacology, University of California San Francisco, San Francisco, CA 94158, USA.
Julien SageDepartment of Pediatrics, Stanford University, 265 Campus Drive, Stanford, CA 94305-5457, USA; Department of Genetics, Stanford University, Stanford, CA 94305, USA. Electronic address: julsage@stanford.edu.
Stanford University · USUniversity of California, San Francisco · USBaxter (United States) · USMichigan Medicine · USUniversity of California, Berkeley · USGladstone Institutes · USPrinceton Satellite Systems (United States) · USQuantitative BioSciences · USUCSF Helen Diller Family Comprehensive Cancer Center · US
Funding
Leveraging innovative technologies in basic and clinical cancer researchT32CA009302 · NCI · STANFORD UNIVERSITY · PI LAURA D ATTARDI, Aaron M Newman · 1985 to 2026
$19.1MCoordinating center for the NCI small cell lung cancer research consortiumU24CA213274 · NCI · SLOAN-KETTERING INST CAN RESEARCH · PI Lauren Averett Byers, JOHN D. MINNA · 2017 to 2026
$12.9MSingle-Cell Biology and Data Analysis Shared Resource (SCB-DA SR)U54CA217450 · NCI · VANDERBILT UNIVERSITY · PI WEAVER, ALISSA M · 2018 to 2022
$8.5MRESEARCH TRAINING IN CHEMISTRY AND CHEMICAL BIOLOGYT32GM064337 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI CRAIK, CHARLES SCOTT · 2002 to 2021
$7.8MInvestigating molecular and cellular mechanisms of SCLC development to identify novel therapeutic strategiesR35CA231997 · NCI · STANFORD UNIVERSITY · PI SAGE, JULIEN · 2019 to 2025
$6.2MStanford Training Program in Aging ResearchT32AG047126 · NIA · STANFORD UNIVERSITY · PI VYJEYANTHI S PERIYAKOIL, TONY WYSS-CORAY · 2014 to 2026
$4.3MChemical Probes to Study Formaldehyde BiologyR01ES028096 · NIEHS · UNIVERSITY OF CALIFORNIA BERKELEY · PI Christopher J. Chang · 2017 to 2026
$4.1MIntegrative Program in Complex Biological System (ipCBS)T32EB009383 · NIBIB · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI MARSHALL, WALLACE, WEINER, ORION D · 2009 to 2022
$3.2MMolecular mechanisms of SCLC initiation and detection in mice and humansU01CA231851 · NCI · STANFORD UNIVERSITY · PI KRASNOW, MARK A · 2018 to 2022
$2.9MInhibitors of the G protein GNAS which drives pancreatic tumorigenesisR01CA244550 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI SHOKAT, KEVAN M. · 2020 to 2024
$2.0MSmall Molecule Activators of PP2A (SMAPs) for Prostate Cancer TherapyR01CA181654 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI NARLA, GOUTHAM · 2015 to 2019
$1.9MNotch signaling in small cell lung carcinomaR01CA201513 · NCI · STANFORD UNIVERSITY · PI SAGE, JULIEN · 2016 to 2019
$1.5MHoward Hughes Medical InstituteNCI NIH HHS R01 CA181654NCI NIH HHS R01 CA201513NCI NIH HHS R01 CA244550NCI NIH HHS R35 CA231997NCI NIH HHS T32 CA009302NCI NIH HHS U01 CA231851NCI NIH HHS U24 CA213274NCI NIH HHS U54 CA217450NIA NIH HHS T32 AG047126NIBIB NIH HHS T32 EB009383NIEHS NIH HHS R01 ES028096NIGMS NIH HHS T32 GM064337NIH HHS S10 OD016229
Abstract
Using unbiased kinase profiling, we identified protein kinase A (PKA) as an active kinase in small cell lung cancer (SCLC). Inhibition of PKA activity genetically, or pharmacologically by activation of the PP2A phosphatase, suppresses SCLC expansion in culture and in vivo. Conversely, GNAS (G-protein α subunit), a PKA activator that is genetically activated in a small subset of human SCLC, promotes SCLC development. Phosphoproteomic analyses identified many PKA substrates and mechanisms of action. In particular, PKA activity is required for the propagation of SCLC stem cells in transplantation studies. Broad proteomic analysis of recalcitrant cancers has the potential to uncover targetable signaling networks, such as the GNAS/PKA/PP2A axis in SCLC.
Indexed as
A549 CellsAnimalsAntineoplastic AgentsCell Line, TumorChromograninsCisplatinCyclic AMP-Dependent Protein KinasesGTP-Binding Protein alpha Subunits, GsHumansLung NeoplasmsMice, Inbred NODMice, KnockoutMice, SCIDNeoplastic Stem CellsProtein Phosphatase 2ProteomicsAntineoplastic AgentsChromograninsCisplatinCyclic AMP-Dependent Protein KinasesGNAS protein, humanGTP-Binding Protein alpha Subunits, GsProtein Phosphatase 2cancercancer stem cellsGNASkinaselungneuroendocrinephosphatasePKAPP2AproteomicsSCLC
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