ArticleScience translational medicine2020
PI4KIIIβ is a therapeutic target in chromosome 1q-amplified lung adenocarcinoma.
Erratum issuedOpen access · greenAbstract read
In one paragraph
Article in Science translational medicine, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 49 papers.
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49citing papers in PubMed
3.3field-weighted citation impact, top 7% of its field
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Who cites it
49 citing papers in PubMed, 64 citations in OpenAlex.
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- Osimertinib activates a TGF-β2-dependent secretory program that drives lung adenocarcinoma progression.The Journal of clinical investigation · 2026Article
- A novel prognostic model based on Golgi apparatus-related genes predicts patient survival in glioblastoma.Open medicine (Warsaw, Poland) · 2026Article
- Golgi Drivers of Cancer.Sub-cellular biochemistry · 2026Review
- Golgi Retention and Oncogenic Signaling of KIT Tyrosine Kinase in Gastrointestinal Stromal Tumor.Sub-cellular biochemistry · 2026Review
- Siamese Twins: The Multimodular Mechanisms of Golgi Maturation and Glycan Synthesis Are Coupled at Their Core.Sub-cellular biochemistry · 2026Review
- The nuclear phosphoinositide-p53 signalosome in the regulation of cell motility.Protein & cell · 2025Review
- Monensin suppresses EMT-driven cancer cell motility by inducing Golgi pH-dependent exocytosis of GOLIM4.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Dichotomous roles of ACBD3 in NSCLC growth and metastasis.Oncogene · 2025Article
- The G protein-coupled receptor GPR89A is a novel potential therapeutic target to overcome cisplatin resistance in NSCLC Calu1 cells.The FEBS journal · 2025Article
- Phosphoinositide kinases in cancer: from molecular mechanisms to therapeutic opportunities.Nature reviews. Cancer · 2025Review
- The link between the trans-Golgi network and tumour progression.Molecular biology reports · 2025Review
- Golgiphagy: a novel selective autophagy to the fore.Cell & bioscience · 2024Review
- The cancer-associated secretory phenotype: a new frontier in targeted therapeutics.The Journal of clinical investigation · 2024Review
- Molecular subtype identification and prognosis stratification based on golgi apparatus-related genes in head and neck squamous cell carcinoma.BMC medical genomics · 2024Article
Corrections and comments
- Erratum issued
Authors and funding
35 authors at 6 institutions in 1 country.
Xiaochao TanDepartment of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.ORCID 0000-0002-8603-5700
Priyam BanerjeeDepartment of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.ORCID 0000-0001-9398-9345
Edward A PhamDepartments of Medicine and Microbiology & Immunology, Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, CA 94305, USA.ORCID 0000-0002-7433-3532
Florentine U N RutaganiraHoward Hughes Medical Institute and Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94143, USA.ORCID 0000-0001-5587-1872
Kaustabh BasuDepartments of Medicine and Microbiology & Immunology, Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Neus Bota-RabassedasDepartment of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Hou-Fu GuoDepartment of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.ORCID 0000-0002-3659-9399
Caitlin L GrzeskowiakDepartment of Molecular and Human Genetics, Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA.
Xin LiuDepartment of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Jiang YuDepartment of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Lei ShiDepartment of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.ORCID 0000-0002-6043-8819
David H PengDepartment of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.ORCID 0000-0003-0511-1888
B Leticia RodriguezDepartment of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.ORCID 0000-0001-8406-7509
Jiaqi ZhangDepartment of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.ORCID 0000-0002-2068-4361
Veronica ZhengDepartment of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Dzifa Y DuoseDepartment of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Luisa M SolisDepartment of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.ORCID 0000-0002-1253-630X
Barbara MinoDepartment of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.ORCID 0000-0001-9217-8719
Maria Gabriela RasoDepartment of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.ORCID 0000-0003-2105-5556
Carmen BehrensDepartment of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.ORCID 0000-0003-1905-8061
Ignacio I WistubaDepartment of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.ORCID 0000-0003-3365-6340
Kenneth L ScottDepartment of Molecular and Human Genetics, Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA.
Mark SmithDepartments of Medicine and Microbiology & Immunology, Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, CA 94305, USA.ORCID 0000-0002-0313-5723
Khanh NguyenDepartments of Medicine and Microbiology & Immunology, Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Grace LamDepartments of Medicine and Microbiology & Immunology, Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, CA 94305, USA.ORCID 0000-0001-7508-8666
Ingrid ChoongDepartments of Medicine and Microbiology & Immunology, Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Abhijit MazumdarDepartment of Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Jamal L HillDepartment of Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Don L GibbonsDepartment of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.ORCID 0000-0003-2362-3094
Powel H BrownDepartment of Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.ORCID 0000-0002-3398-163X
William K RussellDepartment of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, TX 77555, USA.ORCID 0000-0003-1931-4555
Kevan ShokatHoward Hughes Medical Institute and Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94143, USA.ORCID 0000-0001-8590-7741
Chad J CreightonDepartment of Medicine, Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA. jkurie@mdanderson.org jeffrey.glenn@stanford.edu creighto@bcm.edu.ORCID 0000-0002-6090-703X
Jeffrey S GlennDepartments of Medicine and Microbiology & Immunology, Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, CA 94305, USA. jkurie@mdanderson.org jeffrey.glenn@stanford.edu creighto@bcm.edu.ORCID 0000-0002-1843-9965
Jonathan M KurieDepartment of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. jkurie@mdanderson.org jeffrey.glenn@stanford.edu creighto@bcm.edu.ORCID 0000-0002-8603-5700
The University of Texas MD Anderson Cancer Center · USStanford Medicine · USBaylor College of Medicine · USHoward Hughes Medical Institute · USThe University of Texas Medical Branch at Galveston · USUnited States Department of Veterans Affairs · US
Funding
Tumor Evolution and Metastasis ProgramP30CA016672 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI Fabien Delerue · 1985 to 2026
$290.8MTumor BiologyP30CA125123 · NCI · BAYLOR COLLEGE OF MEDICINE · PI Michael M Ittmann · 2007 to 2026
$73.9MUNIVERSITY OF TEXAS--SPORE IN LUNG CANCERP50CA070907 · NCI · UT SOUTHWESTERN MEDICAL CENTER · PI HEYMACH, JOHN V., MINNA, JOHN D. · 1996 to 2024
$57.4MTranslational Incubator CoreU19AI109662 · NIAID · STANFORD UNIVERSITY · PI GLENN, JEFFREY S · 2014 to 2019
$28.6MThe PIP2-virus interface and PI 4-kinase: novel biology and validation targetsR01AI099245 · NIAID · STANFORD UNIVERSITY · PI GLENN, JEFFREY S · 2012 to 2016
$5.2MRegulation of lung cancer metastasis through transcriptional control of the Golgi apparatusR01CA211125 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI KURIE, JONATHAN M · 2017 to 2021
$1.8MRegulation of Lung Cancer Metastasis by ZEB1R01CA181184 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI KURIE, JONATHAN M · 2014 to 2018
$1.7MDetermining structural features of a collagen lysyl hydroxylase that promotes lung cancer metastasisK99CA225633 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI GUO, HOUFU · 2018 to 2019
$224kNCI NIH HHS K99 CA225633NCI NIH HHS P30 CA016672NCI NIH HHS P30 CA125123NCI NIH HHS P50 CA070907NCI NIH HHS R01 CA181184NCI NIH HHS R01 CA211125NIAID NIH HHS R01 AI099245NIAID NIH HHS U19 AI109662
Abstract
Heightened secretion of protumorigenic effector proteins is a feature of malignant cells. Yet, the molecular underpinnings and therapeutic implications of this feature remain unclear. Here, we identify a chromosome 1q region that is frequently amplified in diverse cancer types and encodes multiple regulators of secretory vesicle biogenesis and trafficking, including the Golgi-dedicated enzyme phosphatidylinositol (PI)-4-kinase IIIβ (PI4KIIIβ). Molecular, biochemical, and cell biological studies show that PI4KIIIβ-derived PI-4-phosphate (PI4P) synthesis enhances secretion and accelerates lung adenocarcinoma progression by activating Golgi phosphoprotein 3 (GOLPH3)-dependent vesicular release from the Golgi. PI4KIIIβ-dependent secreted factors maintain 1q-amplified cancer cell survival and influence prometastatic processes in the tumor microenvironment. Disruption of this functional circuitry in 1q-amplified cancer cells with selective PI4KIIIβ antagonists induces apoptosis and suppresses tumor growth and metastasis. These results support a model in which chromosome 1q amplifications create a dependency on PI4KIIIβ-dependent secretion for cancer cell survival and tumor progression.
Indexed as
Adenocarcinoma of LungAnimalsChromosomes, Human, Pair 1Enzyme-Linked Immunosorbent AssayGolgi ApparatusHumansIn Vitro TechniquesMembrane ProteinsMicePhosphotransferases (Alcohol Group Acceptor)X-Ray MicrotomographyGOLPH3 protein, humanMembrane ProteinsPhosphotransferases (Alcohol Group Acceptor)PI4KB protein, human
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