PMID- 19834494
OWN - NLM
STAT- MEDLINE
DCOM- 20100615
LR  - 20240323
IS  - 1476-5403 (Electronic)
IS  - 1350-9047 (Print)
IS  - 1350-9047 (Linking)
VI  - 17
IP  - 4
DP  - 2010 Apr
TI  - The receptor for advanced glycation end products (RAGE) sustains autophagy and 
      limits apoptosis, promoting pancreatic tumor cell survival.
PG  - 666-76
LID - 10.1038/cdd.2009.149 [doi]
AB  - Activation of the induced receptor for advanced glycation end products (RAGE) 
      leads to initiation of NF-kappaB and MAP kinase signaling pathways, resulting in 
      propagation and perpetuation of inflammation. RAGE-knockout animals are less 
      susceptible to acute inflammation and carcinogen-induced tumor development. We 
      have reported that most forms of tumor cell death result in release of the RAGE 
      ligand, high-mobility group protein 1 (HMGB1). We now report a novel role for 
      RAGE in the tumor cell response to stress. Targeted knockdown of RAGE in the 
      tumor cell, leads to increased apoptosis, diminished autophagy and decreased 
      tumor cell survival . In contrast, overexpression of RAGE is associated with 
      enhanced autophagy, diminished apoptosis and greater tumor cell viability. RAGE 
      limits apoptosis through a p53-dependent mitochondrial pathway. Moreover, 
      RAGE-sustained autophagy is associated with decreased phosphorylation of 
      mammalian target of rapamycin (mTOR) and increased Beclin-1/VPS34 autophagosome 
      formation. These findings show that the inflammatory receptor, RAGE, has a 
      heretofore unrecognized role in the tumor cell response to stress. Furthermore, 
      these studies establish a direct link between inflammatory mediators in the tumor 
      microenvironment and resistance to programmed cell death. Our data suggest that 
      targeted inhibition of RAGE or its ligands may serve as novel targets to enhance 
      current cancer therapies.
FAU - Kang, R
AU  - Kang R
AD  - Department of Surgery, Hillman Cancer Center, University of Pittsburgh Cancer 
      Institute, Pittsburgh, PA 15232, USA.
FAU - Tang, D
AU  - Tang D
FAU - Schapiro, N E
AU  - Schapiro NE
FAU - Livesey, K M
AU  - Livesey KM
FAU - Farkas, A
AU  - Farkas A
FAU - Loughran, P
AU  - Loughran P
FAU - Bierhaus, A
AU  - Bierhaus A
FAU - Lotze, M T
AU  - Lotze MT
FAU - Zeh, H J
AU  - Zeh HJ
LA  - eng
GR  - P01 CA101944/CA/NCI NIH HHS/United States
GR  - P01 CA101944-05S1/CA/NCI NIH HHS/United States
GR  - 1 PO1 CA 101944-04/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20091016
PL  - England
TA  - Cell Death Differ
JT  - Cell death and differentiation
JID - 9437445
RN  - 0 (Apoptosis Regulatory Proteins)
RN  - 0 (BECN1 protein, human)
RN  - 0 (Beclin-1)
RN  - 0 (HMGB1 Protein)
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (Membrane Proteins)
RN  - 0 (Receptor for Advanced Glycation End Products)
RN  - 0 (Receptors, Immunologic)
RN  - 0 (Tumor Suppressor Protein p53)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.1.1 (mTOR protein, mouse)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Animals
MH  - Apoptosis/*physiology
MH  - Apoptosis Regulatory Proteins/genetics/metabolism
MH  - Autophagy/*physiology
MH  - Beclin-1
MH  - Carcinoma/*metabolism/physiopathology
MH  - Cell Line, Tumor
MH  - Cell Survival/physiology
MH  - HMGB1 Protein/metabolism
MH  - Humans
MH  - Inflammation/immunology
MH  - Intracellular Signaling Peptides and Proteins/genetics/metabolism
MH  - Membrane Proteins/genetics/metabolism
MH  - Mice
MH  - Pancreatic Neoplasms/*metabolism/physiopathology
MH  - Phosphorylation
MH  - Protein Serine-Threonine Kinases/genetics/metabolism
MH  - RNA Interference
MH  - Receptor for Advanced Glycation End Products
MH  - Receptors, Immunologic/genetics/*metabolism
MH  - Stress, Physiological/*physiology
MH  - TOR Serine-Threonine Kinases
MH  - Tumor Suppressor Protein p53/genetics/metabolism
PMC - PMC3417122
MID - NIHMS143869
EDAT- 2009/10/17 06:00
MHDA- 2010/06/16 06:00
PMCR- 2012/08/12
CRDT- 2009/10/17 06:00
PHST- 2009/10/17 06:00 [entrez]
PHST- 2009/10/17 06:00 [pubmed]
PHST- 2010/06/16 06:00 [medline]
PHST- 2012/08/12 00:00 [pmc-release]
AID - cdd2009149 [pii]
AID - 10.1038/cdd.2009.149 [doi]
PST - ppublish
SO  - Cell Death Differ. 2010 Apr;17(4):666-76. doi: 10.1038/cdd.2009.149. Epub 2009 
      Oct 16.