PMID- 24100703
OWN - NLM
STAT- MEDLINE
DCOM- 20141112
LR  - 20211203
IS  - 1555-8576 (Electronic)
IS  - 1538-4047 (Print)
IS  - 1538-4047 (Linking)
VI  - 15
IP  - 2
DP  - 2014 Feb
TI  - AMP-activated protein kinase (AMPK) beyond metabolism: a novel genomic stress 
      sensor participating in the DNA damage response pathway.
PG  - 156-69
LID - 10.4161/cbt.26726 [doi]
AB  - 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.
FAU - Sanli, Toran
AU  - Sanli T
AD  - Translational Radiation Biology Laboratory; Juravinski Cancer Center; Hamilton, 
      ON Canada; Department of Oncology; McMaster University; Hamilton, ON Canada.
FAU - Steinberg, Gregory R
AU  - Steinberg GR
AD  - Department of Medicine; McMaster University; Hamilton, ON Canada.
FAU - Singh, Gurmit
AU  - Singh G
AD  - Department of Pathology and Molecular Medicine; McMaster University; Hamilton, ON 
      Canada.
FAU - Tsakiridis, Theodoros
AU  - Tsakiridis T
AD  - Translational Radiation Biology Laboratory; Juravinski Cancer Center; Hamilton, 
      ON Canada; Department of Oncology; McMaster University; Hamilton, ON Canada.
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20131101
PL  - United States
TA  - Cancer Biol Ther
JT  - Cancer biology & therapy
JID - 101137842
RN  - 0 (Antineoplastic Agents)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (Ataxia Telangiectasia Mutated Proteins)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - EC 2.7.11.31 (AMP-Activated Protein Kinases)
SB  - IM
MH  - AMP-Activated Protein Kinases/genetics/*metabolism
MH  - Animals
MH  - Antineoplastic Agents/pharmacology/therapeutic use
MH  - Ataxia Telangiectasia Mutated Proteins/metabolism
MH  - Autophagy/drug effects/radiation effects
MH  - Cell Cycle
MH  - Cell Proliferation/drug effects/radiation effects
MH  - *DNA Damage
MH  - Gene Expression Regulation
MH  - Genomic Instability/drug effects/radiation effects
MH  - Humans
MH  - Mitosis/drug effects/radiation effects
MH  - Neoplasms/genetics/*metabolism/pathology/therapy
MH  - Radiation Tolerance
MH  - Signal Transduction
MH  - TOR Serine-Threonine Kinases/metabolism
PMC - PMC3928130
OTO - NOTNLM
OT  - AMPK
OT  - ATM
OT  - cell cycle
OT  - ionizing radiation
OT  - mitosis
EDAT- 2013/10/09 06:00
MHDA- 2014/11/13 06:00
PMCR- 2013/11/01
CRDT- 2013/10/09 06:00
PHST- 2013/10/09 06:00 [entrez]
PHST- 2013/10/09 06:00 [pubmed]
PHST- 2014/11/13 06:00 [medline]
PHST- 2013/11/01 00:00 [pmc-release]
AID - 26726 [pii]
AID - 2013CBT6618 [pii]
AID - 10.4161/cbt.26726 [doi]
PST - ppublish
SO  - Cancer Biol Ther. 2014 Feb;15(2):156-69. doi: 10.4161/cbt.26726. Epub 2013 Nov 1.