ArticleNature cancer2024
Lymphatic endothelial-like cells promote glioblastoma stem cell growth through cytokine-driven cholesterol metabolism.
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Article in Nature cancer, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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42citing papers in PubMed
9.9field-weighted citation impact, top 1% of its field
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Who cites it
42 citing papers in PubMed, 42 citations in OpenAlex.
- VCP-Regulated LMF2 Stabilizes the Cholesterol Biosynthesis Enzyme HMGCS1 to Drive Cancer Progression and Confer Capecitabine Resistance in Triple-Negative Breast Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Low-Density Lipoprotein Receptor-Targeted Biomimetic Nanoplatform Suppresses Glioblastoma Stemness and Remodels Antitumor Immunity via Dual Metabolic Disruption.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Nanotechnology-enabled precision targeting of lung cancer stem cells: Recent developments and therapeutic implications.Stem cell reviews and reports · 2026Review
- Glioma microenvironment: Cellular crosstalk, immunosuppression, and novel therapeutic perspectives.Chinese medical journal · 2026Review
- Early SOX9 Activation Primes Hippo-YAP/TAZ Rewiring During Glioblastoma Stemness Acquisition.Journal of cellular and molecular medicine · 2026Article
- The intersection of chemokine signaling with the hallmarks of cancer in glioblastoma.Journal of neuro-oncology · 2026Review
- CD11b agonist GB1275 potentiates oncolytic bacterial therapy against pancreatic cancer in mouse tumor models.Nature communications · 2026Article
- CCR7-PERK-CREB3L1 signaling mediates tumor-associated macrophages-derived SPP1 promotion of oral squamous cell carcinoma.Communications biology · 2026Article
- Thr3/Ser90 phosphorylation-stabilized S100A8 regulates cholesterol metabolism in glioblastoma stem cells.Oncogene · 2026Article
- The metabolic plasticity of cancer stem cells: bidirectional crosstalk with organ-resident cells.Experimental & molecular medicine · 2026Review
- The vascular niche: an orchestrator of the spatiotemporal dynamics of distant metastasis.Acta pharmacologica Sinica · 2026Review
- Complex I protein NDUFB9 is a metabolic vulnerability in triple negative breast cancer brain metastases.Nature communications · 2026Article
- Glioblastoma Stem Cells and Tumour Microenvironment: Interactions Across Hypoxia, Vasculature and Immune Modulation.International journal of molecular sciences · 2026Review
- The Natural Triterpenoid Alisol B Overcomes Temozolomide Resistance in Glioblastoma Through Multi-Target Mechanisms: Coordinated Epigenetic, Metabolic, and Cell-Cycle Reprogramming.International journal of molecular sciences · 2026Article
- A Supramolecular Nanoscavengers: Based "Cargo-Exchange" Breaking Cholesterol Metabolic Dysregulation for Glioblastoma Therapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Stable isotope tracing in human plasma-like medium reveals metabolic and immune modulation of the glioblastoma microenvironment.Neuro-oncology · 2026Article
- Adaptaquin is selectively toxic to glioma stem cells through disruption of iron and cholesterol metabolism.Molecular oncology · 2026Article
- SAGA/ATAC complexes sustain aberrant chromatin regulation and promote tumorigenesis in diffuse midline glioma.bioRxiv : the preprint server for biology · 2026Article
- Spatial omics at the forefront: emerging technologies, analytical innovations, and clinical applications.Cancer cell · 2026Review
- Endothelial PROX1 induces blood-brain barrier disruption in the central nervous system.JCI insight · 2026Article
Corrections and comments
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Authors and funding
34 authors at 15 institutions in 4 countries.
Linjie Zhao *University of Pittsburgh Medical Center, Hillman Cancer Center, Pittsburgh, PA, USA.
Zhixin Qiu *University of Pittsburgh Medical Center, Hillman Cancer Center, Pittsburgh, PA, USA.ORCID http://orcid.org/0000-0001-7103-8004
Zhengnan Yang *Department of Obstetrics and Gynecology, Key Laboratory of Birth Defects and Related Diseases of Women and Children of the Ministry of Education, and State Key Laboratory of Biotherapy, West China Second Hospital, Sichuan University, and Collaborative Innovation Center, Chengdu, China.
Lian XuDepartment of Pathology, West China Second Hospital, Sichuan University, Chengdu, China.
Thomas M PearceDepartment of Pathology, Division of Neuropathology, University of Pittsburgh, Pittsburgh, PA, USA.ORCID http://orcid.org/0000-0002-5712-9492
Qiulian WuUniversity of Pittsburgh Medical Center, Hillman Cancer Center, Pittsburgh, PA, USA.
Kailin YangDepartment of Radiation Oncology, Taussig Cancer Center, Cleveland Clinic, Cleveland, OH, USA.
FuLong LiDepartment of Pharmacology and Moores Cancer Center, University of California, San Diego, La Jolla, CA, USA.
Olivier SaulnierThe Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, Ontario, Canada.ORCID http://orcid.org/0000-0003-4111-1017
Fan FeiDepartment of Neurosurgery, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chinese Academy of Sciences Sichuan Translational Medicine Research Hospital, Chengdu, China.
Huaxu YuDepartment of Chemistry, University of British Columbia, Vancouver, British Columbia, Canada.ORCID http://orcid.org/0000-0002-2755-8325
Ryan C GimpleDepartment of Pathology, School of Medicine, Case Western Reserve University, Cleveland, OH, USA.ORCID http://orcid.org/0000-0002-7189-3243
Venkateshwari VaradharajanDepartment of Cardiovascular and Metabolic Sciences, Lerner Research Institute Cleveland Clinic, Cleveland, OH, USA.
Juxiu LiuDivision of Obstetrics, Key Laboratory of Birth Defects and Related Disease of Women and Children of MOE, State Key Laboratory of Biotherapy, West China Second Hospital, Sichuan University, Chengdu, China.
Liam D HendrikseThe Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, Ontario, Canada.
Vernon FongThe Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, Ontario, Canada.ORCID http://orcid.org/0000-0003-4064-8066
Wei WangDepartment of Gynecology, Huzhou Maternity & Child Health Care Hospital, Huzhou, China.
Jiao ZhangThe Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, Ontario, Canada.
Deguan LvUniversity of Pittsburgh Medical Center, Hillman Cancer Center, Pittsburgh, PA, USA.
Derrick LeeUniversity of Pittsburgh Medical Center, Hillman Cancer Center, Pittsburgh, PA, USA.
Brandon M LehrichUniversity of Pittsburgh Medical Center, Hillman Cancer Center, Pittsburgh, PA, USA.
Chunyu JinHoward Hughes Medical Institute, Department of Medicine, University of California, San Diego, La Jolla, CA, USA.
Liang OuyangState Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Collaborative Innovation Center for Biotherapy, Chengdu, China.
Deobrat DixitDivision of Regenerative Medicine, Department of Medicine, University of California, San Diego, La Jolla, CA, USA.
Haoxing WuHuaxi MR Research Center, Department of Radiology, Functional and Molecular Imaging Key Laboratory of Sichuan Province, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, China.
Xiang WangDivision of Obstetrics, Key Laboratory of Birth Defects and Related Disease of Women and Children of MOE, State Key Laboratory of Biotherapy, West China Second Hospital, Sichuan University, Chengdu, China.
Andrew E SloanDepartment of Neurosurgery, Case Western Reserve University, Cleveland, OH, USA.
Xiuxing WangSchool of Basic Medical Sciences, Nanjing Medical University, Nanjing, China.ORCID http://orcid.org/0000-0002-5993-9368
Tao HuanDepartment of Chemistry, University of British Columbia, Vancouver, British Columbia, Canada.ORCID http://orcid.org/0000-0001-6295-2435
J Mark BrownDepartment of Cardiovascular and Metabolic Sciences, Lerner Research Institute Cleveland Clinic, Cleveland, OH, USA.ORCID http://orcid.org/0000-0003-2708-7487
Steven A GoldmanUniversity of Rochester Medical Center, Rochester, NY, USA.ORCID http://orcid.org/0000-0002-5498-4303
Michael D TaylorThe Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, Ontario, Canada.ORCID http://orcid.org/0000-0001-7009-3466
Shengtao ZhouDepartment of Obstetrics and Gynecology, Key Laboratory of Birth Defects and Related Diseases of Women and Children of the Ministry of Education, and State Key Laboratory of Biotherapy, West China Second Hospital, Sichuan University, and Collaborative Innovation Center, Chengdu, China. taotaovip2005@163.com.ORCID http://orcid.org/0000-0001-8322-5536
Jeremy N RichUniversity of Pittsburgh Medical Center, Hillman Cancer Center, Pittsburgh, PA, USA. drjeremyrich@gmail.com.ORCID http://orcid.org/0000-0001-7845-5302
Sichuan University · CNUPMC Hillman Cancer Center · USHospital for Sick Children · CAUniversity of California San Diego · USCase Western Reserve University · USCleveland Clinic Lerner College of Medicine · USUniversity of British Columbia · CAUniversity of Toronto · CACleveland Clinic · USFudan University · CNHoward Hughes Medical Institute · USHuzhou Women and Children's Hospital · CNUniversity of Copenhagen · DKUniversity of Electronic Science and Technology of China · CNUniversity of Pittsburgh · US
Funding
Dynamic Complexity of Brain Tumor Stem Cells (R35CA197718)R35CA197718 · NCI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI RICH, JEREMY N · 2015 to 2021
$6.4MMetabolic Regulation of Glioblastoma EpitranscriptomicsR01CA268634 · NCI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI Sameer Agnihotri, JEREMY N RICH · 2022 to 2026
$2.9MMetaorganismal Endocrinology in Cardiometabolic DiseaseR01DK130227 · NIDDK · CLEVELAND CLINIC LERNER COM-CWRU · PI Jonathan Mark Brown · 2021 to 2026
$2.8MTargeting the Circadian Rhythm in Glioblastoma Stem Cells (R01CA238662)R01CA238662 · NCI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI KAY, STEVE A, RICH, JEREMY N · 2020 to 2024
$2.8MTRANSCRIPTIONAL DETERMINANTS OF THE FATE TRAJECTORIES OF SINGLE HUMAN GLIAL PROGENITOR CELLS IN RESPONSE TO DEMYELINATION IN VIVOR01NS110776 · NINDS · UNIVERSITY OF ROCHESTER · PI GOLDMAN, STEVEN ALAN · 2019 to 2023
$1.8MDual Targeting of Brain Tumor Initiating Cells through Inhibition of BMI1 and EZH2 (R01NS103434)R01NS103434 · NINDS · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI RICH, JEREMY N · 2017 to 2021
$1.7MCell-intrinsic and contextual determinants of aging by human glial progenitor cellsR01AG072298 · NIA · UNIVERSITY OF ROCHESTER · PI GOLDMAN, STEVEN ALAN · 2021 to 2025
$1.6MEpigenetic Regulation of Lipid Metabolism in Glioma Stem CellsF30CA217065 · NCI · CLEVELAND CLINIC LERNER COM-CWRU · PI GIMPLE, RYAN CHRISTOPHER · 2017 to 2020
$189kTargeting brain tumor initiating cell-specific super-enhancer associated genes to treat glioblastomaF31CA243296 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI LEE, DERRICK · 2019 to 2022
$147kNational Natural Science Foundation of China (National Science Foundation of China) 81821002National Natural Science Foundation of China (National Science Foundation of China) 81822034National Natural Science Foundation of China (National Science Foundation of China) 82273255National Natural Science Foundation of China (National Science Foundation of China) 82273473NINDS NIH HHS R01 NS110776Shanghai Municipal Health Bureau (Shanghai Municipal Public Health Bureau) 2022YQ062U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) CA094186U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) CA197718U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) CA217065U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) CA238662U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) CA243296U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) CA268634U.S. Department of Health & Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (National Institute of Diabetes & Digestive & Kidney Diseases) DK130227U.S. Department of Health & Human Services | NIH | National Institute of Neurological Disorders and Stroke (NINDS) NS103434U.S. Department of Health & Human Services | NIH | National Institute of Neurological Disorders and Stroke (NINDS) NS110776U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging) AG072298
Abstract
Glioblastoma is the most lethal primary brain tumor with glioblastoma stem cells (GSCs) atop a cellular hierarchy. GSCs often reside in a perivascular niche, where they receive maintenance cues from endothelial cells, but the role of heterogeneous endothelial cell populations remains unresolved. Here, we show that lymphatic endothelial-like cells (LECs), while previously unrecognized in brain parenchyma, are present in glioblastomas and promote growth of CCR7-positive GSCs through CCL21 secretion. Disruption of CCL21-CCR7 paracrine communication between LECs and GSCs inhibited GSC proliferation and growth. LEC-derived CCL21 induced KAT5-mediated acetylation of HMGCS1 on K273 in GSCs to enhance HMGCS1 protein stability. HMGCS1 promoted cholesterol synthesis in GSCs, favorable for tumor growth. Expression of the CCL21-CCR7 axis correlated with KAT5 expression and HMGCS1
Indexed as
Brain NeoplasmsGlioblastomaCell ProliferationCholesterolCytokinesEndothelial CellsHumansNeoplastic Stem CellsReceptors, CCR7CholesterolCytokinesReceptors, CCR7
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