Cited by 220Metabolism, Diabetes, and CancerPI3K/AKT/mTOR signaling in cancerCancer, Hypoxia, and Metabolism

AMP-activated protein kinase (AMPK) beyond metabolism: A novel genomic stress sensor participating in the DNA damage response pathway

Open access
Sanli, Toran, Steinberg, Gregory R, Singh, Gurmit, Tsakiridis, Theodoros·2014·Cancer Biology & Therapy

Abstract

AMP-activated protein kinase (AMPK), an established metabolic stress sensor, has gained popularity in cancer biology due to its ability to control cellular growth and mediate cell cycle checkpoints in cancer cells in response to low energy levels. AMPK is a key effector of the tumor suppressor liver kinase B 1 (LKB1) which inhibits the cellular growth mediator mammalian target of rapamycin (mTOR) and activates checkpoint mediators such as p53 and the cyclin dependent kinase inhibitors p21(cip1) and p27(kip1). However, recent work describes a novel function for AMPK as a sensor of genomic stress and a participant of the DNA damage response (DDR) pathway. Ionizing radiation and chemotherapy activate AMPK in cancer cells to mediate signal transduction downstream of ataxia telangiectasia mutated (ATM) to activate p53- p21(cip1)/p27(kip1) and inhibit mTOR. We discuss evidence on the transcriptional and post-translational regulation of AMPK by ionizing radiation and the role of the enzyme as a mediator of chemo- and radiation sensitivity in epithelial cancer cells. Furthermore, we review data on the participation of AMPK in cytokinesis and observations suggesting a physical association of this enzyme with the mitotic apparatus. The evidence available to date suggests that AMPK is a point of convergence of metabolic and genomic stress signals, which (1) control the activity of growth mediators, (2) propagate DDR, and (3) mediate the anti-proliferative effects of common cytotoxic cancer therapy such as radiation and chemotherapy. This highlights the importance of targeting AMPK with novel cancer therapeutics.

Integrity signals

Registry

Crossref · 10.4161/cbt.26726

Cites

107 of 107 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

We couldn’t retrieve this paper’s full text, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • mTORC1 activation via glutaminolysis suppresses autophagy and the DNA damage response.

    “In addition, mTORC1 activation via glutaminolysis suppresses autophagy and the DNA damage response164,165.”

    From Glutamine reliance in cell metabolism (2020) · cites this paper as [164]

Cites

1 retracted

Flagged first, then by citations

1 of the 108 references couldn’t be matched to a known paper.

Cited by

Sorted by citations

Authors
Sanli, T., Steinberg, G. R., Singh, G., & Tsakiridis, T.
Affiliations
  • Juravinski Cancer Centre (CA)
  • McMaster University (CA)
Corresponding author
Tsakiridis, Theodoros
Venue
Cancer Biology & Therapy
Published
2013-11
Volume
15
Issue
2
Pages
156-169
ISSN
  • 1538-4047 (ISSN-L)
  • 1555-8576
OpenAlex
W1982047458
Cited by
220
References
108
Citations by year
2026: 12 · 2025: 16 · 2024: 9 · 2023: 14 · 2022: 18 · 2021: 16 · 2020: 20 · 2019: 19 · 2018: 13 · 2017: 23 · 2016: 28 · 2015: 18 · 2014: 11 · 2013: 2
FWCI
1.85
Type
journal article
Language
en
Open access
Licence
cc-by-nc
Locations
  • Cancer Biology & Therapy (publishedVersion, cc-by-nc)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
Keywords
AMPK, genomic stress, DNA damage response, ionizing radiation, chemosensitivity, ATM, p53, p21, p27, mTOR, LKB1, cell cycle checkpoints, cytokinesis, mitotic spindle, cancer metabolism, epithelial cancer cells, cancer therapeutics
MeSH terms
Animals, Antineoplastic Agents, Autophagy, Cell Cycle, DNA Damage, Gene Expression Regulation, Humans, Mitosis, Neoplasms, Radiation Tolerance, Signal Transduction, Genomic Instability, Cell Proliferation, AMP-Activated Protein Kinases, TOR Serine-Threonine Kinases, Ataxia Telangiectasia Mutated Proteins

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review