mTOR inhibition induces upstream receptor tyrosine kinase signaling and activates Akt

O'Reilly KE, Rosen N et al. · 2006 · Cancer research · Atlas ID ORE2006

What this study shows

mTORC1 inhibition relieves feedback and activates upstream RTK-PI3K-Akt signalling.

Abstract

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Stimulation of the insulin and insulin-like growth factor I (IGF-I) receptor activates the phosphoinositide-3-kinase/Akt/mTOR pathway causing pleiotropic cellular effects including an mTOR-dependent loss in insulin receptor substrate-1 expression leading to feedback down-regulation of signaling through the pathway. In model systems, tumors exhibiting mutational activation of phosphoinositide-3-kinase/Akt kinase, a common event in cancers, are hypersensitive to mTOR inhibitors, including rapamycin.

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: Cancer cells) 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
Journal	Cancer research
Year	2006
Peer reviewed	Yes
Record last updated	2026-08-22
Source	DOI 10.1158/0008-5472.CAN-05-2925 · PMID 16452206 · Free full text (PMC3193604)

Extracted findings

Intervention	mTOR inhibition (rapamycin)
Target	mTOR / IRS-1 / Akt / RTK
Model	Cancer cells
Effect	mTOR inhibition relieves feedback and induces upstream RTK signaling → activates Akt (a resistance mechanism)

In the Atlas

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Cite this paper

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O'Reilly, K. E., et al. (2006). mTOR inhibition induces upstream receptor tyrosine kinase signaling and activates Akt. Cancer research. https://doi.org/10.1158/0008-5472.CAN-05-2925

@article{ORE2006,
  author       = {O'Reilly, K. E. and Rosen, N. and others},
  title        = {{mTOR inhibition induces upstream receptor tyrosine kinase signaling and activates Akt}},
  journal      = {Cancer research},
  year         = {2006},
  doi          = {10.1158/0008-5472.CAN-05-2925},
  note         = {PMID: 16452206},
}

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 ORE2006) [Data set]. https://mtor-atlas.org/study/ORE2006/ · Dataset DOI 10.5281/zenodo.22059963

@misc{atlas_ORE2006,
  author       = {Barton, Oliver},
  title        = {{Oliver's mTOR Atlas}, record ORE2006},
  howpublished = {Data set},
  year         = {2026},
  url          = {https://mtor-atlas.org/study/ORE2006/},
  doi          = {10.5281/zenodo.22059963}
}