Genetic dissection of the oncogenic mTOR pathway reveals druggable addiction to translational control via 4EBP-eIF4E

Hsieh AC, Costa M, Zollo O, Davis C, Feldman ME, Testa JR, Meyuhas O, Shokat KM, Ruggero D · 2010 · Cancer cell · Atlas ID HSI2010

What this study shows

Genetic dissection shows the 4E-BP1-eIF4E axis mediates oncogenic mTOR signalling and is druggable.

Abstract

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We genetically dissect the contribution of the most prominent downstream translational components of mTOR signaling toward Akt-driven lymphomagenesis. While phosphorylation of rpS6 is dispensable for cancer formation, 4EBP-eIF4E exerts significant control over cap-dependent translation, cell growth, cancer initiation, and progression. This effect is mediated at least in part through 4EBP-dependent control of Mcl-1 expression, a key antiapoptotic protein. By using an active site inhibitor of mTOR, PP242, we show a marked therapeutic response in rapamycin-resistant tumors.

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At a glance

Evidence type	M Molecular — cells, biochemistry, structure Marked M because it is molecular or in-vitro work (model: Cancer cells; mouse) 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	Cancer cells; mouse
Journal	Cancer cell
Year	2010
Peer reviewed	Yes
Record last updated	2026-10-01
Source	DOI 10.1016/j.ccr.2010.01.021 · PMID 20227039 · Free full text (PMC2901095)

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	Genetic dissection (4EBP-eIF4E, rpS6)
Target	mTOR / 4EBP-eIF4E
Model	Cancer cells; mouse
Effect	4EBP-eIF4E (not rpS6) controls cap-dependent translation driving Akt lymphomagenesis – a druggable addiction

In the Atlas

Links in the pathway map

Supports mTORC1 activates Tumor growth

Cite this paper

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Hsieh, A. C., Costa, M., Zollo, O., Davis, C., Feldman, M. E., Testa, J. R., Meyuhas, O., Shokat, K. M., & Ruggero, D. (2010). Genetic dissection of the oncogenic mTOR pathway reveals druggable addiction to translational control via 4EBP-eIF4E. Cancer cell. https://doi.org/10.1016/j.ccr.2010.01.021

@article{HSI2010,
  author       = {Hsieh, A. C. and Costa, M. and Zollo, O. and Davis, C. and Feldman, M. E. and Testa, J. R. and Meyuhas, O. and Shokat, K. M. and Ruggero, D.},
  title        = {{Genetic dissection of the oncogenic mTOR pathway reveals druggable addiction to translational control via 4EBP-eIF4E}},
  journal      = {Cancer cell},
  year         = {2010},
  doi          = {10.1016/j.ccr.2010.01.021},
  note         = {PMID: 20227039},
}

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 HSI2010) [Data set]. https://mtor-atlas.org/study/HSI2010/ · Dataset DOI 10.5281/zenodo.22059963

@misc{atlas_HSI2010,
  author       = {Barton, Oliver},
  title        = {{Oliver's mTOR Atlas}, record HSI2010},
  howpublished = {Data set},
  year         = {2026},
  url          = {https://mtor-atlas.org/study/HSI2010/},
  doi          = {10.5281/zenodo.22059963}
}

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