A nano-liquid hub integrating growth and immune-evasion signaling to promote cell survival

A nano-liquid hub integrating growth and immune-evasion signaling to promote cell survival | bioRxiv Skip to main content Home About Submit ALERTS / RSS Search for this keyword Advanced Search New Results A nano-liquid hub integrating growth and immune-evasion signaling to promote cell survival View ORCID Profile Taka A. Tsunoyama , View ORCID Profile Christian Hoffmann , Daiki Sasaki , Cheng Tan , Bo Tang , View ORCID Profile Koichiro M. Hirosawa , View ORCID Profile Yuri L. Nemoto , View ORCID Profile Rinshi S. Kasai , View ORCID Profile Takahiro K. Fujiwara , Kenichi G. N. Suzuki , View ORCID Profile Yuji Sugita , Hiroki Ishikawa , View ORCID Profile Dragomir Milovanovic , View ORCID Profile Akihiro Kusumi doi: https://doi.org/10.1101/2021.12.30.474523 Taka A. Tsunoyama 1 Membrane Cooperativity Unit, Okinawa Institute of Science and Technology Graduate University (OIST) ; Onna-son, Okinawa, 904-0495, Japan Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Taka A. Tsunoyama For correspondence: taka-aki.tsunoyama{at}oist.jp akihiro.kusumi{at}oist.jp Christian Hoffmann 2 Institute of Biochemistry, Charité - Berlin University of Medicine ; Berlin, 10117, Germany Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Christian Hoffmann Daiki Sasaki 3 Immune Signal Unit, Okinawa Institute of Science and Technology Graduate University (OIST) ; Onna-son, Okinawa, 904-0495, Japan Find this author on Google Scholar Find this author on PubMed Search for this author on this site Cheng Tan 4 Computational Biophysics Research Team, RIKEN Center for Computational Science; Kobe , Hyogo, 650-0047, Japan Find this author on Google Scholar Find this author on PubMed Search for this author on this site Bo Tang 1 Membrane Cooperativity Unit, Okinawa Institute of Science and Technology Graduate University (OIST) ; Onna-son, Okinawa, 904-0495, Japan Find this author on Google Scholar Find this author on PubMed Search for this author on this site Koichiro M. Hirosawa 5 Institute for Glyco-Core Research (iGCORE), Gifu University; Gifu , 501-1193, Japan Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Koichiro M. Hirosawa Yuri L. Nemoto 6 Biosignal Research Center, Kobe University; Kobe , Hyogo, 657-8501, Japan 7 Department of Biochemistry and Molecular Biology, Kobe University Graduate School of Medicine; Kobe , Hyogo, 650-0017, Japan Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Yuri L. Nemoto Rinshi S. Kasai 8 Division of Advanced Bioimaging, National Cancer Center Research Institute; Tokyo , 104-0045, Japan Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Rinshi S. Kasai Takahiro K. Fujiwara 9 Institute for Integrated Cell-Material Sciences (WPI-iCeMS), Kyoto University; Kyoto , 606-8501, Japan Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Takahiro K. Fujiwara Kenichi G. N. Suzuki 5 Institute for Glyco-Core Research (iGCORE), Gifu University; Gifu , 501-1193, Japan 8 Division of Advanced Bioimaging, National Cancer Center Research Institute; Tokyo , 104-0045, Japan 9 Institute for Integrated Cell-Material Sciences (WPI-iCeMS), Kyoto University; Kyoto , 606-8501, Japan Find this author on Google Scholar Find this author on PubMed Search for this author on this site Yuji Sugita 4 Computational Biophysics Research Team, RIKEN Center for Computational Science; Kobe , Hyogo, 650-0047, Japan 10 Theoretical Molecular Science Laboratory, RIKEN Pioneering Research Institute; Wako , Saitama, 351-0198, Japan 11 Department of Physics, University of Tokyo; Tokyo 113–0033 , Japan Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Yuji Sugita Hiroki Ishikawa 3 Immune Signal Unit, Okinawa Institute of Science and Technology Graduate University (OIST) ; Onna-son, Okinawa, 904-0495, Japan Find this author on Google Scholar Find this author on PubMed Search for this author on this site Dragomir Milovanovic 2 Institute of Biochemistry, Charité - Berlin University of Medicine ; Berlin, 10117, Germany Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Dragomir Milovanovic Akihiro Kusumi 1 Membrane Cooperativity Unit, Okinawa Institute of Science and Technology Graduate University (OIST) ; Onna-son, Okinawa, 904-0495, Japan 9 Institute for Integrated Cell-Material Sciences (WPI-iCeMS), Kyoto University; Kyoto , 606-8501, Japan Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Akihiro Kusumi For correspondence: taka-aki.tsunoyama{at}oist.jp akihiro.kusumi{at}oist.jp Abstract Full Text Info/History Metrics Supplementary material Preview PDF Abstract Cell survival in immune-competent organisms relies on both growth and immune evasion, yet these processes have been studied as independent cellular programs. Here, using super-resolution single-molecule imaging, we identify GEM (Growth and Evasion Metastable hub), a ≈34-nm, metastable, nano-liquid, plasma membrane hub that physically integrates receptor-type tyrosine kinase (RTK) inputs with CD59-mediated immune-evasion signaling within the same assembly. GEM is formed by LLPS-like protein clustering on PI(4,5)P 2 -containing raft-nanodomains. Upon concurrent RTK and CD59 stimulations, GEM recruits both receptors and downstream kinases, enabling reciprocal activation via nano-liquid confinement that supralinearly amplifies PLCγ–IP 3 –Ca 2+ and PI3K–Akt survival signaling outputs. In mice, disrupting GEM suppresses tumor growth in vivo , establishing nano-liquid GEM as an integrator that physically couples growth and CD59-mediated immune-evasion signaling for cell survival. Competing Interest Statement The authors have declared no competing interest. Footnotes The whole structure was updated to clarify. Copyright The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license . Back to top Previous Next Posted March 18, 2026. Download PDF Supplementary Material Email Thank you for your interest in spreading the word about bioRxiv. NOTE: Your email address is requested solely to identify you as the sender of this article. Your Email * Your Name * Send To * Enter multiple addresses on separate lines or separate them with commas. You are going to email the following A nano-liquid hub integrating growth and immune-evasion signaling to promote cell survival Message Subject (Your Name) has forwarded a page to you from bioRxiv Message Body (Your Name) thought you would like to see this page from the bioRxiv website. Your Personal Message CAPTCHA This question is for testing whether or not you are a human visitor and to prevent automated spam submissions. 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Suzuki , Yuji Sugita , Hiroki Ishikawa , Dragomir Milovanovic , Akihiro Kusumi bioRxiv 2021.12.30.474523; doi: https://doi.org/10.1101/2021.12.30.474523 Citation Manager Formats BibTeX Bookends EasyBib EndNote (tagged) EndNote 8 (xml) Medlars Mendeley Papers RefWorks Tagged Ref Manager RIS Zotero Tweet Widget Facebook Like Google Plus One Subject Area Cell Biology Subject Areas All Articles Animal Behavior and Cognition (7984) Biochemistry (18689) Bioengineering (14808) Bioinformatics (44286) Biophysics (22532) Cancer Biology (19654) Cell Biology (26817) Clinical Trials (138) Developmental Biology (13916) Ecology (20946) Epidemiology (2067) Evolutionary Biology (25400) Genetics (16132) Genomics (23443) Immunology (18643) Microbiology (42363) Molecular Biology (18003) Neuroscience (93167) Paleontology (696) Pathology (2974) Pharmacology and Toxicology (5076) Physiology (8088) Plant Biology (15953) Scientific Communication and Education (2094) Synthetic Biology (4546) Systems Biology (10205) Zoology (2381)

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