ArticleJournal of the National Cancer Institute2015
Role of LKB1-CRTC1 on glycosylated COX-2 and response to COX-2 inhibition in lung cancer.
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Article in Journal of the National Cancer Institute, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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32citing papers in PubMed
3.7field-weighted citation impact, top 8% of its field
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The trial behind it
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Who cites it
32 citing papers in PubMed, 44 citations in OpenAlex.
- Trial
- Targeting LKB1-inactivated lung cancers with a stapled peptide inhibitor of the CRTC-CREB pathway.Molecular therapy. Oncology · 2026Article
- Divergent Clinical and Immunologic Outcomes Based on STK11 Co-mutation Status in Resectable KRAS-Mutant Lung Cancers Following Neoadjuvant Immune Checkpoint Blockade.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Article
- CRTC1 enhances PD-L1-mediated tumor immunosuppression in non-small cell lung cancer via the Notch1/Akt signaling pathway.Frontiers in immunology · 2025Article
- CRTC1 is a potential target to delay aging-induced cognitive deficit by protecting the integrity of the blood-brain barrier via inhibiting inflammation.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2023Review
- Opportunities and Challenges of Kava in Lung Cancer Prevention.International journal of molecular sciences · 2023Review
- RAD6 Positively Affects Tumorigenesis of Esophageal Squamous Cell Carcinoma by Regulating Histone Ubiquitination of CCNB1.Biological procedures online · 2022Article
- Prioritization and functional analysis of GWAS risk loci for Barrett's esophagus and esophageal adenocarcinoma.Human molecular genetics · 2022Article
- Article
- Dependency of human and murine LKB1-inactivated lung cancer on aberrant CRTC-CREB activation.eLife · 2021Article
- Review
- The Anti-Cancer Effects of a Zotarolimus and 5-Fluorouracil Combination Treatment on A549 Cell-Derived Tumors in BALB/c Nude Mice.International journal of molecular sciences · 2021Article
- The VIM-AS1/miR-655/ZEB1 axis modulates bladder cancer cell metastasis by regulating epithelial-mesenchymal transition.Cancer cell international · 2021Article
- The TGF-β1/COX-2-dependant pathway serves a key role in the generation of OKC-induced M2-polarized macrophage-like cells and angiogenesis.Oncology letters · 2020Article
- Article
- The CREB coactivator CRTC2 promotes oncogenesis in LKB1-mutant non-small cell lung cancer.Science advances · 2019Article
- Role of INSL4 Signaling in Sustaining the Growth and Viability of LKB1-Inactivated Lung Cancer.Journal of the National Cancer Institute · 2019Article
- Adaptive Transcriptional Responses by CRTC Coactivators in Cancer.Trends in cancer · 2019Review
- Interplay between post-translational cyclooxygenase-2 modifications and the metabolic and proteomic profile in a colorectal cancer cohort.World journal of gastroenterology · 2019Article
- A perspective profile of ADCY1 in cAMP signaling with drug-resistance in lung cancer.Journal of Cancer · 2019Review
Corrections and comments
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Authors and funding
15 authors at 6 institutions in 1 country.
Chunxia CaoDepartment of Medicine (CC, RG, MZ, FJK), Genetics Institute (RG, FJK), Genetics and Genomics Graduate Program (RG, FJK), and Molecular Genetics and Microbiology (ZC, YG, CH, LW), University of Florida, Gainesville, FL; Department of Cancer Biology and Informatics, the Scripps Research Institute, Jupiter, FL (ALA, MF); Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC (ALA); Department of Molecular Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL (CH); Cancer Informatics Core (EAW), Department of Molecular Oncology (BEE, WDC), and Department of Thoracic Oncology (EBH), Moffitt Cancer Center, Tampa, FL; Department of Anatomy and Cell Biology, University of Florida, Gainesville, FL (MZK).
Ruli GaoDepartment of Medicine (CC, RG, MZ, FJK), Genetics Institute (RG, FJK), Genetics and Genomics Graduate Program (RG, FJK), and Molecular Genetics and Microbiology (ZC, YG, CH, LW), University of Florida, Gainesville, FL; Department of Cancer Biology and Informatics, the Scripps Research Institute, Jupiter, FL (ALA, MF); Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC (ALA); Department of Molecular Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL (CH); Cancer Informatics Core (EAW), Department of Molecular Oncology (BEE, WDC), and Department of Thoracic Oncology (EBH), Moffitt Cancer Center, Tampa, FL; Department of Anatomy and Cell Biology, University of Florida, Gainesville, FL (MZK).
Min ZhangDepartment of Medicine (CC, RG, MZ, FJK), Genetics Institute (RG, FJK), Genetics and Genomics Graduate Program (RG, FJK), and Molecular Genetics and Microbiology (ZC, YG, CH, LW), University of Florida, Gainesville, FL; Department of Cancer Biology and Informatics, the Scripps Research Institute, Jupiter, FL (ALA, MF); Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC (ALA); Department of Molecular Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL (CH); Cancer Informatics Core (EAW), Department of Molecular Oncology (BEE, WDC), and Department of Thoracic Oncology (EBH), Moffitt Cancer Center, Tampa, FL; Department of Anatomy and Cell Biology, University of Florida, Gainesville, FL (MZK).
Antonio L AmelioDepartment of Medicine (CC, RG, MZ, FJK), Genetics Institute (RG, FJK), Genetics and Genomics Graduate Program (RG, FJK), and Molecular Genetics and Microbiology (ZC, YG, CH, LW), University of Florida, Gainesville, FL; Department of Cancer Biology and Informatics, the Scripps Research Institute, Jupiter, FL (ALA, MF); Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC (ALA); Department of Molecular Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL (CH); Cancer Informatics Core (EAW), Department of Molecular Oncology (BEE, WDC), and Department of Thoracic Oncology (EBH), Moffitt Cancer Center, Tampa, FL; Department of Anatomy and Cell Biology, University of Florida, Gainesville, FL (MZK).
Mohammad FallahiDepartment of Medicine (CC, RG, MZ, FJK), Genetics Institute (RG, FJK), Genetics and Genomics Graduate Program (RG, FJK), and Molecular Genetics and Microbiology (ZC, YG, CH, LW), University of Florida, Gainesville, FL; Department of Cancer Biology and Informatics, the Scripps Research Institute, Jupiter, FL (ALA, MF); Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC (ALA); Department of Molecular Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL (CH); Cancer Informatics Core (EAW), Department of Molecular Oncology (BEE, WDC), and Department of Thoracic Oncology (EBH), Moffitt Cancer Center, Tampa, FL; Department of Anatomy and Cell Biology, University of Florida, Gainesville, FL (MZK).
Zirong ChenDepartment of Medicine (CC, RG, MZ, FJK), Genetics Institute (RG, FJK), Genetics and Genomics Graduate Program (RG, FJK), and Molecular Genetics and Microbiology (ZC, YG, CH, LW), University of Florida, Gainesville, FL; Department of Cancer Biology and Informatics, the Scripps Research Institute, Jupiter, FL (ALA, MF); Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC (ALA); Department of Molecular Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL (CH); Cancer Informatics Core (EAW), Department of Molecular Oncology (BEE, WDC), and Department of Thoracic Oncology (EBH), Moffitt Cancer Center, Tampa, FL; Department of Anatomy and Cell Biology, University of Florida, Gainesville, FL (MZK).
Yumei GuDepartment of Medicine (CC, RG, MZ, FJK), Genetics Institute (RG, FJK), Genetics and Genomics Graduate Program (RG, FJK), and Molecular Genetics and Microbiology (ZC, YG, CH, LW), University of Florida, Gainesville, FL; Department of Cancer Biology and Informatics, the Scripps Research Institute, Jupiter, FL (ALA, MF); Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC (ALA); Department of Molecular Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL (CH); Cancer Informatics Core (EAW), Department of Molecular Oncology (BEE, WDC), and Department of Thoracic Oncology (EBH), Moffitt Cancer Center, Tampa, FL; Department of Anatomy and Cell Biology, University of Florida, Gainesville, FL (MZK).
Chengbin HuDepartment of Medicine (CC, RG, MZ, FJK), Genetics Institute (RG, FJK), Genetics and Genomics Graduate Program (RG, FJK), and Molecular Genetics and Microbiology (ZC, YG, CH, LW), University of Florida, Gainesville, FL; Department of Cancer Biology and Informatics, the Scripps Research Institute, Jupiter, FL (ALA, MF); Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC (ALA); Department of Molecular Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL (CH); Cancer Informatics Core (EAW), Department of Molecular Oncology (BEE, WDC), and Department of Thoracic Oncology (EBH), Moffitt Cancer Center, Tampa, FL; Department of Anatomy and Cell Biology, University of Florida, Gainesville, FL (MZK).
Eric A WelshDepartment of Medicine (CC, RG, MZ, FJK), Genetics Institute (RG, FJK), Genetics and Genomics Graduate Program (RG, FJK), and Molecular Genetics and Microbiology (ZC, YG, CH, LW), University of Florida, Gainesville, FL; Department of Cancer Biology and Informatics, the Scripps Research Institute, Jupiter, FL (ALA, MF); Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC (ALA); Department of Molecular Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL (CH); Cancer Informatics Core (EAW), Department of Molecular Oncology (BEE, WDC), and Department of Thoracic Oncology (EBH), Moffitt Cancer Center, Tampa, FL; Department of Anatomy and Cell Biology, University of Florida, Gainesville, FL (MZK).
Brienne E EngelDepartment of Medicine (CC, RG, MZ, FJK), Genetics Institute (RG, FJK), Genetics and Genomics Graduate Program (RG, FJK), and Molecular Genetics and Microbiology (ZC, YG, CH, LW), University of Florida, Gainesville, FL; Department of Cancer Biology and Informatics, the Scripps Research Institute, Jupiter, FL (ALA, MF); Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC (ALA); Department of Molecular Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL (CH); Cancer Informatics Core (EAW), Department of Molecular Oncology (BEE, WDC), and Department of Thoracic Oncology (EBH), Moffitt Cancer Center, Tampa, FL; Department of Anatomy and Cell Biology, University of Florida, Gainesville, FL (MZK).
Eric B HauraDepartment of Medicine (CC, RG, MZ, FJK), Genetics Institute (RG, FJK), Genetics and Genomics Graduate Program (RG, FJK), and Molecular Genetics and Microbiology (ZC, YG, CH, LW), University of Florida, Gainesville, FL; Department of Cancer Biology and Informatics, the Scripps Research Institute, Jupiter, FL (ALA, MF); Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC (ALA); Department of Molecular Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL (CH); Cancer Informatics Core (EAW), Department of Molecular Oncology (BEE, WDC), and Department of Thoracic Oncology (EBH), Moffitt Cancer Center, Tampa, FL; Department of Anatomy and Cell Biology, University of Florida, Gainesville, FL (MZK).
W Douglas CressDepartment of Medicine (CC, RG, MZ, FJK), Genetics Institute (RG, FJK), Genetics and Genomics Graduate Program (RG, FJK), and Molecular Genetics and Microbiology (ZC, YG, CH, LW), University of Florida, Gainesville, FL; Department of Cancer Biology and Informatics, the Scripps Research Institute, Jupiter, FL (ALA, MF); Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC (ALA); Department of Molecular Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL (CH); Cancer Informatics Core (EAW), Department of Molecular Oncology (BEE, WDC), and Department of Thoracic Oncology (EBH), Moffitt Cancer Center, Tampa, FL; Department of Anatomy and Cell Biology, University of Florida, Gainesville, FL (MZK).
Lizi WuDepartment of Medicine (CC, RG, MZ, FJK), Genetics Institute (RG, FJK), Genetics and Genomics Graduate Program (RG, FJK), and Molecular Genetics and Microbiology (ZC, YG, CH, LW), University of Florida, Gainesville, FL; Department of Cancer Biology and Informatics, the Scripps Research Institute, Jupiter, FL (ALA, MF); Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC (ALA); Department of Molecular Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL (CH); Cancer Informatics Core (EAW), Department of Molecular Oncology (BEE, WDC), and Department of Thoracic Oncology (EBH), Moffitt Cancer Center, Tampa, FL; Department of Anatomy and Cell Biology, University of Florida, Gainesville, FL (MZK).
Maria Zajac-KayeDepartment of Medicine (CC, RG, MZ, FJK), Genetics Institute (RG, FJK), Genetics and Genomics Graduate Program (RG, FJK), and Molecular Genetics and Microbiology (ZC, YG, CH, LW), University of Florida, Gainesville, FL; Department of Cancer Biology and Informatics, the Scripps Research Institute, Jupiter, FL (ALA, MF); Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC (ALA); Department of Molecular Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL (CH); Cancer Informatics Core (EAW), Department of Molecular Oncology (BEE, WDC), and Department of Thoracic Oncology (EBH), Moffitt Cancer Center, Tampa, FL; Department of Anatomy and Cell Biology, University of Florida, Gainesville, FL (MZK).
Frederic J KayeDepartment of Medicine (CC, RG, MZ, FJK), Genetics Institute (RG, FJK), Genetics and Genomics Graduate Program (RG, FJK), and Molecular Genetics and Microbiology (ZC, YG, CH, LW), University of Florida, Gainesville, FL; Department of Cancer Biology and Informatics, the Scripps Research Institute, Jupiter, FL (ALA, MF); Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC (ALA); Department of Molecular Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL (CH); Cancer Informatics Core (EAW), Department of Molecular Oncology (BEE, WDC), and Department of Thoracic Oncology (EBH), Moffitt Cancer Center, Tampa, FL; Department of Anatomy and Cell Biology, University of Florida, Gainesville, FL (MZK). fkaye@ufl.edu.
University of Florida · USMolecular Oncology (United States) · USScripps Research Institute · USUniversity of North Carolina at Chapel Hill · USMoffitt Cancer Center · USUniversity of South Florida · US
Funding
TRANSLATIONAL RESEARCHP30CA076292 · NCI · UNIVERSITY OF SOUTH FLORIDA · PI KENNETH Lynn WRIGHT · 1998 to 2026
$93.5MUsing MC1R genotype to impact skin cancer risk behaviors in Hispanics/LatinosU54CA163068 · NCI · H. LEE MOFFITT CANCER CTR & RES INST · PI KENNETH Lynn WRIGHT · 2012 to 2026
$23.1MUsing MC1R genotype to impact skin cancer risk behaviors in Hispanics/LatinosU54CA163071 · NCI · PONCE SCHOOL OF MEDICINE · PI Luisa Morales-Torres · 2012 to 2026
$23.0MSPORE in Lung CancerP50CA119997 · NCI · H. LEE MOFFITT CANCER CTR & RES INST · PI GABRILOVICH, DMITRY I · 2008 to 2012
$11.0MSignaling and Targeting of CRTC1-MAML2 Fusion Oncoprotein in Salivary Gland TumorR01DE023641 · NIDCR · UNIVERSITY OF FLORIDA · PI Lizi Wu · 2014 to 2026
$3.3MIntegrative Molecular Epidemiology WorkshopR25CA174664 · NCI · AMERICAN ASSOCIATION FOR CANCER RESEARCH · PI Shelley S Tworoger · 2013 to 2026
$2.8MConvergence of CREB and MYC Pathways in Oncogenesis.R00CA157954 · NCI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI AMELIO, ANTONIO LUIGI · 2014 to 2016
$740kConvergence of CREB and MYC Pathways in Oncogenesis.K99CA157954 · NCI · SCRIPPS FLORIDA · PI AMELIO, ANTONIO LUIGI · 2012 to 2013
$294kNCI NIH HHS K99 CA157954NCI NIH HHS K99-CA157954NCI NIH HHS P30 CA076292NCI NIH HHS P50 CA119997NCI NIH HHS R00 CA157954NCI NIH HHS R25 CA174664NCI NIH HHS U54 CA163068NIDCR NIH HHS R01 DE023641
Abstract
backgroundCyclooxygenase-2 (COX-2) directs the synthesis of prostaglandins including PGE-2 linking inflammation with mitogenic signaling. COX-2 is also an anticancer target, however, treatment strategies have been limited by unreliable expression assays and by inconsistent tumor responses to COX-2 inhibition.
methodsWe analyzed the TCGA and Director's Challenge lung cancer datasets (n = 188) and also generated an LKB1-null lung cancer gene signature (n = 53) to search the Broad Institute/Connectivity-MAP (C-MAP) dataset. We performed ChIP analyses, real-time polymerase chain reaction, immunoblotting, and drug testing of tumor cell lines (n = 8) and primary lung adenocarcinoma surgical resections (n = 13).
resultsWe show that COX-2 is a target of the cAMP/CREB coactivator CRTC1 signaling pathway. In addition, we detected a correlation between LKB1 status, CRTC1 activation, and presence of glycosylated, but not inactive hypoglycosylated COX-2 in primary lung adenocarcinoma. A search of the C-MAP drug database discovered that all high-ranking drugs positively associated with the LKB1-null signature are known CRTC1 activators, including forskolin and six different PGE-2 analogues. Somatic LKB1 mutations are present in 20.0% of lung adenocarcinomas, and we observed growth inhibition with COX-2 inhibitors in LKB1-null lung cancer cells with activated CRTC1 as compared with LKB1-wildtype cells (NS-398, P = .002 and Niflumic acid, P = .006; two-tailed t test).
conclusionCRTC1 activation is a key event that drives the LKB1-null mRNA signature in lung cancer. We also identified a positive feedback LKB1/CRTC1 signaling loop for COX-2/PGE2 regulation. These data suggest a role for LKB1 status and glycosylated COX-2 as specific biomarkers that provide a framework for selecting patients for COX-2 inhibition studies.
Indexed as
AdenocarcinomaAdenocarcinoma of LungAMP-Activated Protein Kinase KinasesAntineoplastic AgentsCell Line, TumorCyclic AMPCyclooxygenase 2Cyclooxygenase 2 InhibitorsDinoprostoneEsophageal NeoplasmsFluorescent Antibody TechniqueGlycosylationHumansImmunoblottingLung NeoplasmsPatient SelectionAMP-Activated Protein Kinase KinasesAntineoplastic AgentsCRTC1 protein, humanCyclic AMPCyclooxygenase 2Cyclooxygenase 2 InhibitorsDinoprostoneProtein Serine-Threonine KinasesPTGS2 protein, humanSTK11 protein, humanTranscription Factors
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