PMID- 22785201
OWN - NLM
STAT- MEDLINE
DCOM- 20121214
LR  - 20221207
IS  - 1555-8576 (Electronic)
IS  - 1538-4047 (Print)
IS  - 1538-4047 (Linking)
VI  - 13
IP  - 10
DP  - 2012 Aug
TI  - HuR's post-transcriptional regulation of Death Receptor 5 in pancreatic cancer 
      cells.
PG  - 946-55
LID - 10.4161/cbt.20952 [doi]
AB  - Apoptosis is one of the core signaling pathways disrupted in pancreatic ductal 
      adenocarcinoma (PDA). Death receptor 5 (DR5) is a member of the tumor necrosis 
      factor (TNF)-receptor superfamily that is expressed in cancer cells. Binding of 
      TNF-related apoptosis-inducing ligand (TRAIL) to DR5 is a potent trigger of the 
      extrinsic apoptotic pathway, and numerous clinical trials are based on 
      DR5-targeted therapies for cancer, including PDA. Human antigen R (HuR), an 
      RNA-binding protein, regulates a select number of transcripts under stress 
      conditions. Here we report that HuR translocates from the nucleus to the 
      cytoplasm of PDA cells upon treatment with a DR5 agonist. High doses of DR5 
      agonist induce cleavage of both HuR and caspase 8. HuR binds to DR5 mRNA at the 
      5'-untranslated region (UTR) in PDA cells in response to different 
      cancer-associated stressors and subsequently represses DR5 protein expression; 
      silencing HuR augments DR5 protein production by enabling its translation and 
      thus enhances apoptosis. In PDA specimens (n = 53), negative HuR cytoplasmic 
      expression correlated with elevated DR5 expression (odds ratio 16.1, p < 0.0001). 
      Together, these data demonstrate a feedback mechanism elicited by HuR-mediated 
      repression of the key apoptotic membrane protein DR5.
FAU - Pineda, Danielle M
AU  - Pineda DM
AD  - Department of Surgery, Division of Surgical Research, Jefferson Medical College, 
      Thomas Jefferson University, Philadelphia, PA, USA.
FAU - Rittenhouse, David W
AU  - Rittenhouse DW
FAU - Valley, Christopher C
AU  - Valley CC
FAU - Cozzitorto, Joseph A
AU  - Cozzitorto JA
FAU - Burkhart, Richard A
AU  - Burkhart RA
FAU - Leiby, Benjamin
AU  - Leiby B
FAU - Winter, Jordan M
AU  - Winter JM
FAU - Weber, Matthew C
AU  - Weber MC
FAU - Londin, Eric R
AU  - Londin ER
FAU - Rigoutsos, Isidore
AU  - Rigoutsos I
FAU - Yeo, Charles J
AU  - Yeo CJ
FAU - Gorospe, Myriam
AU  - Gorospe M
FAU - Witkiewicz, Agnieska K
AU  - Witkiewicz AK
FAU - Sachs, Jonathan N
AU  - Sachs JN
FAU - Brody, Jonathan R
AU  - Brody JR
LA  - eng
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20120801
PL  - United States
TA  - Cancer Biol Ther
JT  - Cancer biology & therapy
JID - 101137842
RN  - 0 (5' Untranslated Regions)
RN  - 0 (Antimetabolites, Antineoplastic)
RN  - 0 (ELAV Proteins)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, TNF-Related Apoptosis-Inducing Ligand)
RN  - 0W860991D6 (Deoxycytidine)
RN  - 0 (Gemcitabine)
SB  - IM
MH  - 5' Untranslated Regions
MH  - Antimetabolites, Antineoplastic/pharmacology
MH  - Cell Line, Tumor
MH  - Cytoplasm/metabolism
MH  - Deoxycytidine/analogs & derivatives/pharmacology
MH  - ELAV Proteins/genetics/*metabolism
MH  - Gene Expression Regulation, Neoplastic
MH  - Gene Silencing
MH  - Humans
MH  - Pancreatic Neoplasms/*genetics/*metabolism
MH  - Protein Transport/drug effects
MH  - Proteolysis/drug effects
MH  - *RNA Processing, Post-Transcriptional
MH  - RNA, Messenger
MH  - Receptors, TNF-Related Apoptosis-Inducing Ligand/agonists/*genetics/metabolism
MH  - Gemcitabine
PMC - PMC3414415
EDAT- 2012/07/13 06:00
MHDA- 2012/12/15 06:00
PMCR- 2013/08/01
CRDT- 2012/07/13 06:00
PHST- 2012/07/13 06:00 [entrez]
PHST- 2012/07/13 06:00 [pubmed]
PHST- 2012/12/15 06:00 [medline]
PHST- 2013/08/01 00:00 [pmc-release]
AID - 20952 [pii]
AID - 2012CBT5745 [pii]
AID - 10.4161/cbt.20952 [doi]
PST - ppublish
SO  - Cancer Biol Ther. 2012 Aug;13(10):946-55. doi: 10.4161/cbt.20952. Epub 2012 Aug 
      1.