The LKB1 tumor suppressor negatively regulates mTOR signaling

Shaw RJ, Bardeesy N, Manning BD, Lopez L, Kosmatka M, DePinho RA, Cantley LC · 2004 · Cancer Cell · Atlas ID SHAW2004

What this study shows

Reported that LKB1 is needed to switch mTOR signalling off when cellular ATP falls, and that this requires AMPK and TSC2. Lkb1-null fibroblasts and the hamartomatous gut polyps of Lkb1 mutant mice showed raised signalling downstream of mTOR. The authors proposed mTOR inhibitors as a treatment idea for Peutz-Jeghers syndrome. Published alongside Corradetti et al. 2004, which reached the same LKB1-AMPK-TSC2 link independently. Boundary: worked from the abstract only (no PMC full text); cell and mouse data, the treatment suggestion was not tested here.

Abstract

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Germline mutations in LKB1, TSC2, or PTEN tumor suppressor genes result in hamartomatous syndromes with shared tumor biological features. The recent observations of LKB1-mediated activation of AMP-activated protein kinase (AMPK) and AMPK inhibition of mTOR through TSC2 prompted us to examine the biochemical and biological relationship between LKB1 and mTOR regulation.

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: Lkb1-null mouse embryonic fibroblasts; cultured cells under low ATP; gastrointestinal polyps from Lkb1 mutant mice) 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	Lkb1-null mouse embryonic fibroblasts; cultured cells under low ATP; gastrointestinal polyps from Lkb1 mutant mice
Journal	Cancer Cell
Year	2004
Peer reviewed	Yes
Record last updated	2026-10-01
Source	DOI 10.1016/j.ccr.2004.06.007 · PMID 15261145

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	Lkb1 deletion; energy stress (low ATP)
Target	LKB1 -> AMPK -> TSC2 -> mTOR
Model	Mouse embryonic fibroblasts; Lkb1 mutant mice
Effect	Loss of LKB1 prevents repression of mTOR under low ATP and raises mTOR signalling in polyps

In the Atlas

Cite this paper

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Shaw, R. J., Bardeesy, N., Manning, B. D., Lopez, L., Kosmatka, M., DePinho, R. A., & Cantley, L. C. (2004). The LKB1 tumor suppressor negatively regulates mTOR signaling. Cancer Cell. https://doi.org/10.1016/j.ccr.2004.06.007

@article{SHAW2004,
  author       = {Shaw, R. J. and Bardeesy, N. and Manning, B. D. and Lopez, L. and Kosmatka, M. and DePinho, R. A. and Cantley, L. C.},
  title        = {{The LKB1 tumor suppressor negatively regulates mTOR signaling}},
  journal      = {Cancer Cell},
  year         = {2004},
  doi          = {10.1016/j.ccr.2004.06.007},
  note         = {PMID: 15261145},
}

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 SHAW2004) [Data set]. https://mtor-atlas.org/study/SHAW2004/ · Dataset DOI 10.5281/zenodo.22059963

@misc{atlas_SHAW2004,
  author       = {Barton, Oliver},
  title        = {{Oliver's mTOR Atlas}, record SHAW2004},
  howpublished = {Data set},
  year         = {2026},
  url          = {https://mtor-atlas.org/study/SHAW2004/},
  doi          = {10.5281/zenodo.22059963}
}

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