Uncovering the signaling networks of disseminated glioblastoma cells in vivo with INSIGHT.
Overview
and 6 other authors
Ann Tuma6, Jared L. Johnson13,14, Nathalie Y. R. Agar15,16, Josie Ursini-Siegel17,18, Sarkaria Jann6, Forest M. White1,2,1118 affiliations
- David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology (MIT),Cambridge, MA USA
- Department of Biological Engineering, MIT,Cambridge, MA USA
- MIT-Harvard Health Sciences and Technology,Cambridge, MA USA
- Department of Neurosurgery, Brigham and Women’s Hospital, Harvard Medical School,Boston, MA USA
- Department of Electronic Engineering, Rovira i Virgili University,Tarragona, Spain
- Mayo Clinic,Rochester, MN USA
- MIT,Cambridge, MA USA
- Barbara K. Ostrom (1978) Bioinformatics and Computing Core Facility of the Swanson Biotechnology Center, David H. Koch Institute for Integrative Cancer Research,Cambridge, USA
- Columbia University Vagelos College of Physicians and Surgeons,New York, NY USA
- Microscopy Core Facility of the Swanson Biotechnology Center, David H. Koch Institute for Integrative Cancer Research,Cambridge, USA
- Program in Computational and Systems Biology, MIT,Cambridge, MA USA
- Preclinical Imaging and Testing Facility of the Swanson Biotechnology Center, David H. Koch Institute for Integrative Cancer Research, MIT,Cambridge, MA USA
- Department of Cell Biology, Harvard Medical School,Boston, MA USA
- Dana-Farber Cancer Institute, Harvard Medical School,Boston, MA USA
- Department of Radiology, Brigham and Women’s Hospital, Harvard Medical School,Boston, MA USA
- Department of Cancer Biology, Dana-Farber Cancer Institute,Boston, MA USA
- Division of Experimental Medicine, McGill University,Montreal, QC Canada
- Lady Davis Institute for Medical Research, Jewish General Hospital,Montreal, QC Canada
Abstract
Dysregulation of intracellular signaling networks underpins cancer. Yet, resolving signaling networks within distinct or rare cell types in cancer in vivo has been unattainable. Here we develop INSIGHT by integrating cell sorting with mass spectrometry to enable quantitative phosphoproteomics and proteomics of discrete cell types from fixed tissues. Using INSIGHT, we map the signaling network within disseminating glioblastoma cells from patient-derived xenografts implanted in mice. Disseminating tumor cells undergo a proteome-wide shift from proliferative to mesenchymal, neural progenitor-like cell states. In parallel, signaling network and global kinase activity are rewired, transitioning from cell cycle-associated circuitries to those governing synaptic function, neuronal migration, and ion channel activity. Changes begin at the tumor margin and persist in distant brain parenchyma. Hornerin and phosphorylation of Ca²⁺-permeable GluA2 at Y876 were identified as mediators of glioblastoma progression. INSIGHT enables systems-level dissection of cell-type-specific signaling circuitries in vivo across wide range of biological systems.
Reproduced under the paper's license (CC BY), from the paper cited above.
Code
No file of the authors' code could be read here: it is described below, and read at its source.
cycif.org
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ryuhjinahn
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hub.docker.com/r/bumproo
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Code availability
Codes used in this study are available at https://
Reproduced under the paper's license (CC BY), from the paper cited above.
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Data
Datasets cited
- sra:SRR9294059, at NCBI SRA; found in “Data availability”
Data availability
The mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium via the PRIDE [1] partner repository with the dataset identifier PXD056965 and https://
Reproduced under the paper's license (CC BY), from the paper cited above.
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Version 1, 27 September 2026: the first record
Recorded: type, language, journal, volume, issue, pages, dates, 26 authors, 2 keywords, 12 MeSH terms, 1 funder, 131 references, 1 RRID.
Cite
This paper
Ahn, R., D’Souza, A. D., Long, L., Cui, Y., Gantchev, J., Baquer, G., Burgenske, D., Bakken, K. K., Ott, L. L., Carlson, B. L., Zhou, G., Kohale, I. N., Whittaker, C. A., Temple, H., Yaron-Barir, T. M., Wyckoff, J., Burns, T. C., Vaubel, R. A., Flower, C. T., . . . White, F. M. (2026). Uncovering the signaling networks of disseminated glioblastoma cells in vivo with INSIGHT. Nature communications, 17(1), 9536. https://
BibTeX
@article{ahn2026uncoveri
author = {Ahn, Ryuhjin and D’Souza, Alicia D. and Long, Lawrence and Cui, Yufei and Gantchev, Jennifer and Baquer, Gerard and Burgenske, Danielle and Bakken, Katrina K. and Ott, Lauren L. and Carlson, Brett L. and Zhou, Grace and Kohale, Ishwar N. and Whittaker, Charles A. and Temple, Heidi and Yaron-Barir, Tomer M. and Wyckoff, Jeffrey and Burns, Terry C. and Vaubel, Rachael A. and Flower, Cameron T. and Huang, Wei and Tuma, Ann and Johnson, Jared L. and Agar, Nathalie Y. R. and Ursini-Siegel, Josie and Jann, Sarkaria and White, Forest M.},
title = {{Uncovering the signaling networks of disseminated glioblastoma cells in vivo with INSIGHT}},
journal = {Nature communications},
year = {2026},
month = aug,
volume = {17},
number = {1},
pages = {9536},
publisher = {Nature Publishing Group},
issn = {2041-1723},
doi = {10.1038/
url = {https://
pmid = {42702597},
pmcid = {PMC13547291}
}
RIS
TY - JOUR
AU - Ahn, Ryuhjin
AU - D’Souza, Alicia D.
AU - Long, Lawrence
AU - Cui, Yufei
AU - Gantchev, Jennifer
AU - Baquer, Gerard
AU - Burgenske, Danielle
AU - Bakken, Katrina K.
AU - Ott, Lauren L.
AU - Carlson, Brett L.
AU - Zhou, Grace
AU - Kohale, Ishwar N.
AU - Whittaker, Charles A.
AU - Temple, Heidi
AU - Yaron-Barir, Tomer M.
AU - Wyckoff, Jeffrey
AU - Burns, Terry C.
AU - Vaubel, Rachael A.
AU - Flower, Cameron T.
AU - Huang, Wei
AU - Tuma, Ann
AU - Johnson, Jared L.
AU - Agar, Nathalie Y. R.
AU - Ursini-Siegel, Josie
AU - Jann, Sarkaria
AU - White, Forest M.
TI - Uncovering the signaling networks of disseminated glioblastoma cells in vivo with INSIGHT
T2 - Nature communications
J2 - Nat Commun
PY - 2026
DA - 2026/
VL - 17
IS - 1
SP - 9536
SN - 2041-1723
PB - Nature Publishing Group
DO - 10.1038/
UR - https://
LA - en
ER -
CSL-JSON
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