The translational landscape of mTOR signalling steers cancer initiation and metastasis

Hsieh AC, Liu Yi, Edlind MP, Ingolia NT, Janes MR, Sher A, Shi EY, Stumpf CR, Christensen C, Bonham MJ, Wang S, …, Ruggero D · 2012 · Nature · Atlas ID HSI2012

What this study shows

Showed WHY mTOR-driven translation matters for cancer: in prostate cancer, oncogenic mTOR selectively translates a specific set of pro-invasion mRNAs that drive metastasis. An ATP-competitive mTOR inhibitor (INK128) reversed that signature - an early preclinical rationale from mouse models and cell lines, not a clinical result.

Abstract

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The mammalian target of rapamycin (mTOR) kinase is a master regulator of protein synthesis that couples nutrient sensing to cell growth and cancer. However, the downstream translationally regulated nodes of gene expression that may direct cancer development are poorly characterized. Using ribosome profiling, we uncover specialized translation of the prostate cancer genome by oncogenic mTOR signalling, revealing a remarkably specific repertoire of genes involved in cell proliferation, metabolism and invasion.

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: Mouse models + human prostate cancer) 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	Mouse models + human prostate cancer
Journal	Nature
Year	2012
Peer reviewed	Yes
Record last updated	2026-07-29
Source	DOI 10.1038/nature10912 · PMID 22367541 · Free full text (PMC3663483)

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	Oncogenic mTOR modulation + ribosome profiling
Target	mTOR / 4E-BP–eIF4E translation
Model	Mouse models + human prostate cancer
Effect	Oncogenic mTOR reprograms translation of a specific gene set driving proliferation, metabolism and invasion/metastasis

In the Atlas

Links in the pathway map

Supports eIF4E activates Protein synthesis
Supports mTORC1 activates Tumor growth
Supports mTORC1 activates Ribosome biogenesis
Supports mTORC1 activates 5'TOP mRNA

Cite this paper

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Hsieh, A. C., Liu Yi, Edlind, M. P., Ingolia, N. T., Janes, M. R., Sher, A., Shi, E. Y., Stumpf, C. R., Christensen, C., Bonham, M. J., Wang, S., Ren, P., Martin, M., Jessen, K., Feldman, M. E., Weissman, J. S., Shokat, K. M., Rommel, C., & Ruggero, D. (2012). The translational landscape of mTOR signalling steers cancer initiation and metastasis. Nature. https://doi.org/10.1038/nature10912

@article{HSI2012,
  author       = {Hsieh, A. C. and Liu Yi and Edlind, M. P. and Ingolia, N. T. and Janes, M. R. and Sher, A. and Shi, E. Y. and Stumpf, C. R. and Christensen, C. and Bonham, M. J. and Wang, S. and Ren, P. and Martin, M. and Jessen, K. and Feldman, M. E. and Weissman, J. S. and Shokat, K. M. and Rommel, C. and Ruggero, D.},
  title        = {{The translational landscape of mTOR signalling steers cancer initiation and metastasis}},
  journal      = {Nature},
  year         = {2012},
  doi          = {10.1038/nature10912},
  note         = {PMID: 22367541},
}

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 HSI2012) [Data set]. https://mtor-atlas.org/study/HSI2012/ · Dataset DOI 10.5281/zenodo.22059963

@misc{atlas_HSI2012,
  author       = {Barton, Oliver},
  title        = {{Oliver's mTOR Atlas}, record HSI2012},
  howpublished = {Data set},
  year         = {2026},
  url          = {https://mtor-atlas.org/study/HSI2012/},
  doi          = {10.5281/zenodo.22059963}
}

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