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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.

Tier D because it is mechanistic or in-vitro work (model: Human cancer cell lines (functional genomics/CRISPR screens)), not a whole-organism health-outcome study; tier describes study design, not quality -- this is often exactly where causal biology gets established.

At a glance

Evidence tier	D Mechanistic / in vitro / review
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	2026-08-22
Source	DOI 10.1101/gad.353708.126 · PMID 42575690

Extracted findings

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

Abstract

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 →

Cite this record

Barton, O. (2026). mTOR inactivation governs adaptive survival to ribosome biogenesis deficiency — evidence-graded record FAN2026. In Oliver's mTOR Atlas. https://mtor-atlas.org/study/FAN2026/ · Dataset DOI 10.5281/zenodo.22059963

@misc{atlas_FAN2026,
  author       = {Barton, Oliver},
  title        = {{mTOR inactivation governs adaptive survival to ribosome biogenesis deficiency} --- evidence-graded record FAN2026},
  howpublished = {Oliver's mTOR Atlas},
  year         = {2026},
  url          = {https://mtor-atlas.org/study/FAN2026/},
  note         = {Dataset DOI: 10.5281/zenodo.22059963}
}

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