ArticleDevelopmental cell2025
A forward genetic screen identifies potassium channel essentiality in SHH medulloblastoma maintenance.
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Article in Developmental cell, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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2 citing papers in PubMed.
- Stress granules as a central hub linking organelle stress, aging, and neurodegeneration.BMB reports · 2026Review
- Metastatic medulloblastoma remodels the local leptomeningeal microenvironment to promote further metastatic colonization and growth.Nature cell biology · 2025Article
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Authors and funding
40 authors.
Jerry J FanDevelopmental and Stem Cell Biology Program, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada; Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada; Department of Molecular Genetics, University of Toronto, Toronto, ON M5S 1A8, Canada.
Anders W EricksonDevelopmental and Stem Cell Biology Program, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada; Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada.
Julia Carrillo-GarciaDevelopmental and Stem Cell Biology Program, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada; Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada.
Xin WangDevelopmental and Stem Cell Biology Program, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada; Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada.
Patryk SkowronDevelopmental and Stem Cell Biology Program, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada; Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada.
Xian WangDevelopmental and Stem Cell Biology Program, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada; Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada; Department of Mechanical and Industrial Engineering, University of Toronto, Toronto, ON M5S 3E1, Canada.
Xin ChenDevelopmental and Stem Cell Biology Program, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada; Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada; Songjiang Research Institute, Shanghai Key Laboratory of Emotions and Affective Disorders, Songjiang Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200032, China.
Guanqiao ShanDepartment of Mechanical and Industrial Engineering, University of Toronto, Toronto, ON M5S 3E1, Canada.
Wenkun DouDepartment of Mechanical and Industrial Engineering, University of Toronto, Toronto, ON M5S 3E1, Canada.
Shahrzad BahrampourDevelopmental and Stem Cell Biology Program, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada; Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada.
Yi XiongDevelopmental and Stem Cell Biology Program, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada; Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada; Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China; Hunan International Scientific and Technological Cooperation Base of Brain Tumor Research, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.
Weifan DongDevelopmental and Stem Cell Biology Program, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada; Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada; Department of Molecular Genetics, University of Toronto, Toronto, ON M5S 1A8, Canada.
Namal AbeysundaraDevelopmental and Stem Cell Biology Program, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada; Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada.
Michelle A FranciscoDevelopmental and Stem Cell Biology Program, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada; Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada.
Ronwell J PusongDevelopmental and Stem Cell Biology Program, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada; Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada.
Wei WangDevelopmental and Stem Cell Biology Program, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada; Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada.
Miranda LiDevelopmental and Stem Cell Biology Program, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada; Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada.
Elliot YingDevelopmental and Stem Cell Biology Program, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada; Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada.
Raúl A SuárezDevelopmental and Stem Cell Biology Program, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada; Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada.
Hamza FarooqDevelopmental and Stem Cell Biology Program, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada; Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON M5S 3E1, Canada.
Borja L HolgadoDevelopmental and Stem Cell Biology Program, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada; Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada.
Xiaochong WuDevelopmental and Stem Cell Biology Program, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada; Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada; Texas Children's Cancer and Hematology Center, Houston, TX 77030, USA; Department of Pediatrics, Hematology/Oncology, Baylor College of Medicine, Houston, TX 77030, USA.
Craig DanielsDevelopmental and Stem Cell Biology Program, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada; Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada; Texas Children's Cancer and Hematology Center, Houston, TX 77030, USA; Department of Pediatrics, Hematology/Oncology, Baylor College of Medicine, Houston, TX 77030, USA.
Adam J DupuyDepartment of Anatomy & Cell Biology, Carver College of Medicine, University of Iowa, Iowa City, IA 52246, USA.
Juan CadiñanosInstituto de Medicina Oncológica y Molecular de Asturias (IMOMA), Oviedo 33193, Spain.
Allan BradleyT-Therapeutics Ltd. One Riverside, Granta Park, Cambridge CB21 6AD, UK.
Anindya BagchiTumor Initiation and Maintenance Program, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037, USA.
Branden S MoriarityMasonic Cancer Center, Department of Pediatrics, and Center for Genome Engineering, University of Minnesota, Minneapolis, MN 55455, USA.
David A LargaespadaMasonic Cancer Center, Department of Pediatrics, and Center for Genome Engineering, University of Minnesota, Minneapolis, MN 55455, USA.
A Sorana MorrissyDevelopmental and Stem Cell Biology Program, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada; Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada; Arnie Charbonneau Cancer Institute, University of Calgary, Calgary, AB T2N 4Z6, Canada; Alberta Children's Hospital Research Institute, University of Calgary, Calgary, AB T2N 4N1, Canada; Department of Biochemistry and Molecular Biology, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 2T8, Canada.
Vijay RamaswamyDevelopmental and Stem Cell Biology Program, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada; Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada; Department of Paediatrics, University of Toronto, Toronto, ON M5G 1X8, Canada.
Stephen C MackDevelopmental and Stem Cell Biology Program, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada; Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada; Department of Developmental Neurobiology, Neurobiology and Brain Tumor Program, Center of Excellence in Neuro-Oncology Sciences, St Jude Children's Hospital, Memphis, TN 38105, USA.
Livia GarziaDevelopmental and Stem Cell Biology Program, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada; Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada; Department of Surgery, Division of Orthopedic Surgery, McGill University, Montreal, QC H4A 3J1, Canada; Cancer Research Program, RI-MUHC, Montreal, QC H4A 3J1, Canada.
Peter B DirksDevelopmental and Stem Cell Biology Program, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada; Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada; Department of Molecular Genetics, University of Toronto, Toronto, ON M5S 1A8, Canada; Department of Surgery, University of Toronto, Toronto, ON M5S 1A8, Canada.
Xuejun LiDepartment of Neurosurgery, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China; Hunan International Scientific and Technological Cooperation Base of Brain Tumor Research, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.
Siyi WanggouDevelopmental and Stem Cell Biology Program, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada; Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada; Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China; Hunan International Scientific and Technological Cooperation Base of Brain Tumor Research, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.
Sean EganArthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada; Department of Molecular Genetics, University of Toronto, Toronto, ON M5S 1A8, Canada; Cell Biology Program, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada.
Yu SunDepartment of Mechanical and Industrial Engineering, University of Toronto, Toronto, ON M5S 3E1, Canada.
Michael D TaylorDevelopmental and Stem Cell Biology Program, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada; Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON M5S 3E1, Canada; Department of Surgery, University of Toronto, Toronto, ON M5S 1A8, Canada; Texas Children's Cancer and Hematology Center, Houston, TX 77030, USA; Department of Pediatrics, Hematology/Oncology, Baylor College of Medicine, Houston, TX 77030, USA; Department of Neurosurgery, Baylor College of Medicine, Houston, TX 77030, USA; Department of Neurosurgery, Texas Children's Hospital, Houston, TX 77030, USA; Dan L Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA. Electronic address: mdt.cns@gmail.com.
Xi HuangDevelopmental and Stem Cell Biology Program, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada; Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada; Department of Molecular Genetics, University of Toronto, Toronto, ON M5S 1A8, Canada. Electronic address: xi.huang@sickkids.ca.
Funding
Mouse models to discover new drivers of medulloblastomaR01CA159859 · NCI · SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE · PI Michael D. Taylor, WILLIAM A WEISS · 2011 to 2026
$10.4MCCL2 and CCR2 as metastatic drivers and therapeutic targets in medulloblastomaR01CA255369 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI GARZIA, LIVIA, TAYLOR, MICHAEL D. · 2021 to 2025
$3.9MPrevention and treatment of lethal metastases in group 3 medulloblastomaR01NS106155 · NINDS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI TAYLOR, MICHAEL D., WEISS, WILLIAM A · 2018 to 2022
$2.8MNCI NIH HHS R01 CA159859NCI NIH HHS R01 CA255369NINDS NIH HHS R01 NS106155
Abstract
Distinguishing tumor maintenance genes from initiation, progression, and passenger genes is critical for developing effective therapies. We employed a functional genomic approach using the Lazy Piggy transposon to identify tumor maintenance genes in vivo and applied this to sonic hedgehog (SHH) medulloblastoma (MB). Combining Lazy Piggy screening in mice and transcriptomic profiling of human MB, we identified the voltage-gated potassium channel KCNB2 as a candidate maintenance driver. KCNB2 governs cell volume of MB-propagating cells (MPCs), with KCNB2 depletion causing osmotic swelling, decreased plasma membrane tension, and elevated endocytic internalization of epidermal growth factor receptor (EGFR), thereby mitigating proliferation of MPCs to ultimately impair MB growth. KCNB2 is largely dispensable for mouse development and KCNB2 knockout synergizes with anti-SHH therapy in treating MB. These results demonstrate the utility of the Lazy Piggy functional genomic approach in identifying cancer maintenance drivers and elucidate a mechanism by which potassium homeostasis integrates biomechanical and biochemical signaling to promote MB aggression.
Indexed as
Cerebellar NeoplasmsHedgehog ProteinsMedulloblastomaShab Potassium ChannelsAnimalsCell ProliferationErbB ReceptorsGene Expression Regulation, NeoplasticHumansMiceMice, KnockoutSignal TransductionErbB ReceptorsHedgehog ProteinsShab Potassium Channelsfunctional genomicsinsertional mutagenesisKCNB2mechanobiologymedulloblastomamembrane tensionpediatric brain tumorpotassium channeltransposon
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