mTOR inactivation governs adaptive survival to ribosome biogenesis deficiency

Fan W, Liu H, Yang L, Sinha N, Catipovic M, Dong D, Easawaran H, Green R, Laiho M · 2026 · Genes & Development · Atlas ID FAN2026

What this study shows

mTORC1 inhibition does not restore ribosome biogenesis but redistributes limited ribosomes away from highly-translated 5'TOP mRNAs toward survival-essential transcripts, defining a 'translational fitness' mechanism that lets cancer cells survive ribosome biogenesis deficiency.

Abstract

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Ribosome biogenesis is a resource-consuming process that facilitates rapid growth and feeds uncontrolled, cancerous traits. Constraining ribosome biogenesis and protein translation has become a tenable therapeutic strategy for cancer. Yet, we do not know how cells that rely on high metabolic activity adapt and sustain their growth when deprived of their translational capacity. Conversely, stem cells and treatment-resistant cells persist under low metabolic states challenging their eradication. These are critical questions in cancer therapies.

Read the full abstract on PubMed →

At a glance

Evidence type	M Molecular — cells, biochemistry, structure Marked M because it is molecular or in-vitro work (model: Human cancer cell lines (functional genomics/CRISPR screens)) rather than a whole-organism health-outcome study. That is often exactly where causal biology gets established -- the code says which system the finding was shown in, and nothing about how good the work is.
Study type	5 - Mechanistic / In Vitro
Model system	Human cancer cell lines (functional genomics/CRISPR screens)
Journal	Genes & Development
Year	2026
Peer reviewed	Yes
Record last updated	2026-10-01
Source	DOI 10.1101/gad.353708.126 · PMID 42575690

Extracted findings

These fields were extracted from the paper with AI assistance and have not been checked against the source. Read them as a pointer into the paper, not as curated claims; where they disagree with the curated summary above, the curated summary stands.

Intervention	Functional genomics/CRISPR screens under RNA Pol I inhibition; mTOR inactivation (genetic/pharmacologic)
Target	mTORC1 / ribosome biogenesis / 5'TOP mRNA translation
Model	Human cancer cell lines
Effect	mTOR inactivation redistributes limited ribosomes from 5'TOP mRNAs to survival-essential transcripts, enabling adaptive survival ('translational fitness') under ribosome biogenesis deficiency

In the Atlas

Links in the pathway map

Supports mTORC1 activates Ribosome biogenesis

Cite this paper

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Fan, W., Liu, H., Yang, L., Sinha, N., Catipovic, M., Dong, D., Easawaran, H., Green, R., & Laiho, M. (2026). mTOR inactivation governs adaptive survival to ribosome biogenesis deficiency. Genes & Development. https://doi.org/10.1101/gad.353708.126

@article{FAN2026,
  author       = {Fan, W. and Liu, H. and Yang, L. and Sinha, N. and Catipovic, M. and Dong, D. and Easawaran, H. and Green, R. and Laiho, M.},
  title        = {{mTOR inactivation governs adaptive survival to ribosome biogenesis deficiency}},
  journal      = {Genes & Development},
  year         = {2026},
  doi          = {10.1101/gad.353708.126},
  note         = {PMID: 42575690},
}

Cite this Atlas record

The record is the Atlas's own work — the evidence label, the extracted findings and the links. It is cited as part of the dataset, not as the paper.

Barton, O. (2026). Oliver's mTOR Atlas (record FAN2026) [Data set]. https://mtor-atlas.org/study/FAN2026/ · Dataset DOI 10.5281/zenodo.22059963

@misc{atlas_FAN2026,
  author       = {Barton, Oliver},
  title        = {{Oliver's mTOR Atlas}, record FAN2026},
  howpublished = {Data set},
  year         = {2026},
  url          = {https://mtor-atlas.org/study/FAN2026/},
  doi          = {10.5281/zenodo.22059963}
}

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