Glioblastoma Hijacks Astrocyte Ribosomes to Feul Malignancy through Translatome Reprogramming

Abstract

Cancer cells demand elevated protein synthesis, yet whether they directly requisition ribosomes from microenvironmental host cells remains unknown. Here, utilizing in vivo and in vitro ribosome tracing, we show that glioblastoma (GBM) cells hijack ribosomes from surrounding astrocytes via tunneling nanotube-like structures. This transfer supports GBM malignancy in both murine and patient derived models. Single cell RNA sequencing along with whole cell and cell source traceable ribosome profiling reveal that transferred ribosomes are translationally active and selectively reprogram the tumor translatome, prioritizing cell-cycle genes and driving interferon-response-mediated immune evasion. Through a genome wide CRISPR screen, we identify INTS12 as a critical mediator of ribosome transfer. Genetic inactivation or AAV-mediated knockdown of INTS12 impairs ribosome uptake, curbs translation and proliferation, remodels the immunosuppressive landscape, and extends survival in orthotopic models. Our study uncovers a parasitic translation-support mechanism in GBM, establishing INTS12 as a therapeutic vulnerability to disrupt ribosome transfer.

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BibTeX RIS

BibTeX

@misc{wu2026glioblastoma,
  title = {{Glioblastoma Hijacks Astrocyte Ribosomes to Feul Malignancy through Translatome Reprogramming}},
  author = {X. Wu and C. Zheng and L. Chen and J. Chen and Y. Zhang and L. Cheng and Y. Peng and X. Zeng and M. Gao and F. Luo and Y. Lai and J. Cheng and Y. Gao and J. Zhong and X. Yang and N. Huang and F. Xiao and X. Liu and F. Bai and N. Zhang},
  howpublished = {bioRxiv},
  year = {2026},
  month = oct,
  doi = {10.64898/2026.10.28.762373},
  url = {https://www.biorxiv.org/content/10.64898/2026.10.28.762373v1},
  note = {CC BY},
}

RIS

TY  - UNPB
TI  - Glioblastoma Hijacks Astrocyte Ribosomes to Feul Malignancy through Translatome Reprogramming
AU  - X. Wu
AU  - C. Zheng
AU  - L. Chen
AU  - J. Chen
AU  - Y. Zhang
AU  - L. Cheng
AU  - Y. Peng
AU  - X. Zeng
AU  - M. Gao
AU  - F. Luo
AU  - Y. Lai
AU  - J. Cheng
AU  - Y. Gao
AU  - J. Zhong
AU  - X. Yang
AU  - N. Huang
AU  - F. Xiao
AU  - X. Liu
AU  - F. Bai
AU  - N. Zhang
PY  - 2026
DA  - 2026/10/28
PB  - bioRxiv
DO  - 10.64898/2026.10.28.762373
UR  - https://www.biorxiv.org/content/10.64898/2026.10.28.762373v1
AB  - Cancer cells demand elevated protein synthesis, yet whether they directly requisition ribosomes from microenvironmental host cells remains unknown. Here, utilizing in vivo and in vitro ribosome tracing, we show that glioblastoma (GBM) cells hijack ribosomes from surrounding astrocytes via tunneling nanotube-like structures. This transfer supports GBM malignancy in both murine and patient derived models. Single cell RNA sequencing along with whole cell and cell source traceable ribosome profiling reveal that transferred ribosomes are translationally active and selectively reprogram the tumor translatome, prioritizing cell-cycle genes and driving interferon-response-mediated immune evasion. Through a genome wide CRISPR screen, we identify INTS12 as a critical mediator of ribosome transfer. Genetic inactivation or AAV-mediated knockdown of INTS12 impairs ribosome uptake, curbs translation and proliferation, remodels the immunosuppressive landscape, and extends survival in orthotopic models. Our study uncovers a parasitic translation-support mechanism in GBM, establishing INTS12 as a therapeutic vulnerability to disrupt ribosome transfer.
ER  -

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