Single amino-acid changes that confer constitutive activation of mTOR are discovered in human cancer

Sato T, Nakashima A, Guo L, Coffman K, Tamanoi F · 2010 · Oncogene · Atlas ID SAT2010

What this study shows

Screened point mutations from cancer genome databases and found two, S2215Y (large intestine adenocarcinoma) and R2505P (renal cell carcinoma), that kept mTOR signalling on even under nutrient starvation. mTORC1 purified from starved cells carrying the mutants still phosphorylated 4E-BP1 in vitro. Mutant cells had more S-phase cells (42.0% vs 28.2% for S2215Y) and resisted the shrinkage caused by amino-acid withdrawal. The mutants stayed sensitive to rapamycin. Boundary: overexpressed mutants in cultured cells; the mutations were found in tumour databases, their driver role in patients was not tested.

Abstract

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Mammalian target of rapamycin (mTOR) is a serine/threonine kinase that regulates a variety of cellular functions such as growth, proliferation and autophagy. In a variety of cancer cells, overactivation of mTOR has been reported. In addition, mTOR inhibitors, such as rapamycin and its derivatives, are being evaluated in clinical trials as anticancer drugs. However, no active mutants of mTOR have been identified in human cancer.

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: Cells expressing mTOR point mutants found in cancer genome databases; in vitro kinase assays) 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	Cells expressing mTOR point mutants found in cancer genome databases; in vitro kinase assays
Journal	Oncogene
Year	2010
Peer reviewed	Yes
Record last updated	2026-10-01
Source	DOI 10.1038/onc.2010.28 · PMID 20190810 · Free full text (PMC2953941)

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	Expression of mTOR point mutants S2215Y and R2505P; rapamycin
Target	mTOR kinase / mTORC1
Model	Cultured mammalian cells
Effect	Cancer-derived mTOR mutations make mTORC1 active under starvation; still rapamycin-sensitive

In the Atlas

Links in the pathway map

Supports mTORC1 inhibits 4E-BP1
Supports Rapamycin inhibits mTORC1

Cite this paper

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Sato, T., Nakashima, A., Guo, L., Coffman, K., & Tamanoi, F. (2010). Single amino-acid changes that confer constitutive activation of mTOR are discovered in human cancer. Oncogene. https://doi.org/10.1038/onc.2010.28

@article{SAT2010,
  author       = {Sato, T. and Nakashima, A. and Guo, L. and Coffman, K. and Tamanoi, F.},
  title        = {{Single amino-acid changes that confer constitutive activation of mTOR are discovered in human cancer}},
  journal      = {Oncogene},
  year         = {2010},
  doi          = {10.1038/onc.2010.28},
  note         = {PMID: 20190810},
}

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 SAT2010) [Data set]. https://mtor-atlas.org/study/SAT2010/ · Dataset DOI 10.5281/zenodo.22059963

@misc{atlas_SAT2010,
  author       = {Barton, Oliver},
  title        = {{Oliver's mTOR Atlas}, record SAT2010},
  howpublished = {Data set},
  year         = {2026},
  url          = {https://mtor-atlas.org/study/SAT2010/},
  doi          = {10.5281/zenodo.22059963}
}

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