PMID- 18551130
OWN - NLM
STAT- MEDLINE
DCOM- 20081027
LR  - 20211020
IS  - 1350-9047 (Print)
IS  - 1350-9047 (Linking)
VI  - 15
IP  - 10
DP  - 2008 Oct
TI  - Hypoxia signals autophagy in tumor cells via AMPK activity, independent of HIF-1, 
      BNIP3, and BNIP3L.
PG  - 1572-81
LID - 10.1038/cdd.2008.84 [doi]
AB  - Macroautophagy (called autophagy hereafter) is a catabolic process activated by 
      various types of stress, most notably by nutrient deprivation. The autophagic 
      degradation of intracellular macromolecules provides metabolic support for the 
      cell; however, this physiological process can also initiate a form of cell death 
      (type 2 programmed cell death). Here we report that oxygen deprivation can 
      activate the autophagic pathway in human cancer cell lines. We observed that 
      hypoxia induced distinct cellular changes characteristic of autophagy such as an 
      increase in cytoplasmic acidic vesicles, and processing and cellular localization 
      of microtubule-associated protein-1 light chain 3. Oxygen deprivation-induced 
      autophagy did not require nutrient deprivation, hypoxia-inducible factor-1 
      (HIF-1) activity, or expression of the HIF-1 target gene BNIP3 (Bcl-2 adenovirus 
      E1a nineteen kilodalton interacting protein 3) or BNIP3L (BNIP3 like protein). 
      Hypoxia-induced autophagy involved the activity of 5'-AMP-activated protein 
      kinase (AMPK). Finally, we determined that cells lacking the autophagy gene ATG5 
      were unable to activate the autophagic machinery in hypoxia, had decreased oxygen 
      consumption and increased glucose uptake under hypoxia, had increased survival in 
      hypoxic environments, and exhibited accelerated growth as xenografted tumors. 
      Together, these findings suggest that the autophagic degradation of cellular 
      macromolecules contributes to the energetic balance governed by AMPK, and that 
      suppression of autophagy in transformed cells can increase both resistance to 
      hypoxic stress and tumorigenicity.
FAU - Papandreou, I
AU  - Papandreou I
AD  - Division of Radiation and Cancer Biology, Department of Radiation Oncology, 
      Stanford University School of Medicine, Stanford, CA 94305, USA.
FAU - Lim, A L
AU  - Lim AL
FAU - Laderoute, K
AU  - Laderoute K
FAU - Denko, N C
AU  - Denko NC
LA  - eng
GR  - P01 CA067166/CA/NCI NIH HHS/United States
GR  - P30 CA016058/CA/NCI NIH HHS/United States
GR  - R01 CA163581/CA/NCI NIH HHS/United States
GR  - S10 OD020006/OD/NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20080613
PL  - England
TA  - Cell Death Differ
JT  - Cell death and differentiation
JID - 9437445
RN  - 0 (ATG5 protein, human)
RN  - 0 (Autophagy-Related Protein 5)
RN  - 0 (BNIP3 protein, human)
RN  - 0 (BNIP3L protein, human)
RN  - 0 (HIF1A protein, human)
RN  - 0 (Hypoxia-Inducible Factor 1, alpha Subunit)
RN  - 0 (Membrane Proteins)
RN  - 0 (Microtubule-Associated Proteins)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (Tumor Suppressor Proteins)
RN  - EC 2.7.4.3 (Adenylate Kinase)
RN  - S88TT14065 (Oxygen)
SB  - IM
MH  - Adenylate Kinase/*metabolism
MH  - Animals
MH  - Autophagy/*physiology
MH  - Autophagy-Related Protein 5
MH  - Cell Line, Tumor
MH  - Fibroblasts/cytology/physiology
MH  - Humans
MH  - *Hypoxia
MH  - Hypoxia-Inducible Factor 1, alpha Subunit/genetics/*metabolism
MH  - Membrane Proteins/*metabolism
MH  - Mice
MH  - Mice, Knockout
MH  - Microtubule-Associated Proteins/genetics/metabolism
MH  - Oxygen/metabolism
MH  - Phagosomes/metabolism
MH  - Proto-Oncogene Proteins/*metabolism
MH  - Signal Transduction/physiology
MH  - Tumor Suppressor Proteins/*metabolism
EDAT- 2008/06/14 09:00
MHDA- 2008/10/28 09:00
CRDT- 2008/06/14 09:00
PHST- 2008/06/14 09:00 [pubmed]
PHST- 2008/10/28 09:00 [medline]
PHST- 2008/06/14 09:00 [entrez]
AID - cdd200884 [pii]
AID - 10.1038/cdd.2008.84 [doi]
PST - ppublish
SO  - Cell Death Differ. 2008 Oct;15(10):1572-81. doi: 10.1038/cdd.2008.84. Epub 2008 
      Jun 13.