PMID- 21887346
OWN - NLM
STAT- MEDLINE
DCOM- 20120224
LR  - 20211020
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 6
IP  - 8
DP  - 2011
TI  - SMURF1 amplification promotes invasiveness in pancreatic cancer.
PG  - e23924
LID - 10.1371/journal.pone.0023924 [doi]
LID - e23924
AB  - Pancreatic cancer is a deadly disease, and new therapeutic targets are urgently 
      needed. We previously identified DNA amplification at 7q21-q22 in pancreatic 
      cancer cell lines. Now, by high-resolution genomic profiling of human pancreatic 
      cancer cell lines and human tumors (engrafted in immunodeficient mice to enrich 
      the cancer epithelial fraction), we define a 325 Kb minimal amplicon spanning 
      SMURF1, an E3 ubiquitin ligase and known negative regulator of transforming 
      growth factor beta (TGFbeta) growth inhibitory signaling. SMURF1 amplification was 
      confirmed in primary human pancreatic cancers by fluorescence in situ 
      hybridization (FISH), where 4 of 95 cases (4.2%) exhibited amplification. By RNA 
      interference (RNAi), knockdown of SMURF1 in a human pancreatic cancer line with 
      focal amplification (AsPC-1) did not alter cell growth, but led to reduced cell 
      invasion and anchorage-independent growth. Interestingly, this effect was not 
      mediated through altered TGFbeta signaling, assayed by transcriptional reporter. 
      Finally, overexpression of SMURF1 (but not a catalytic mutant) led to loss of 
      contact inhibition in NIH-3T3 mouse embryo fibroblast cells. Together, these 
      findings identify SMURF1 as an amplified oncogene driving multiple tumorigenic 
      phenotypes in pancreatic cancer, and provide a new druggable target for 
      molecularly directed therapy.
FAU - Kwei, Kevin A
AU  - Kwei KA
AD  - Department of Pathology, Stanford University, Stanford, California, United States 
      of America.
FAU - Shain, A Hunter
AU  - Shain AH
FAU - Bair, Ryan
AU  - Bair R
FAU - Montgomery, Kelli
AU  - Montgomery K
FAU - Karikari, Collins A
AU  - Karikari CA
FAU - van de Rijn, Matt
AU  - van de Rijn M
FAU - Hidalgo, Manuel
AU  - Hidalgo M
FAU - Maitra, Anirban
AU  - Maitra A
FAU - Bashyam, Murali D
AU  - Bashyam MD
FAU - Pollack, Jonathan R
AU  - Pollack JR
LA  - eng
GR  - R01 CA112016/CA/NCI NIH HHS/United States
GR  - P50 CA062924/CA/NCI NIH HHS/United States
GR  - CA62924/CA/NCI NIH HHS/United States
GR  - T32 CA009151/CA/NCI NIH HHS/United States
GR  - UL1 RR025744/RR/NCRR NIH HHS/United States
GR  - UL1 TR001085/TR/NCATS NIH HHS/United States
GR  - CA09151/CA/NCI NIH HHS/United States
GR  - CA112016/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 - 20110822
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - EC 2.3.2.26 (SMURF1 protein, human)
RN  - EC 2.3.2.27 (Ubiquitin-Protein Ligases)
SB  - IM
MH  - Animals
MH  - Cell Communication
MH  - Cell Line
MH  - Cell Line, Tumor
MH  - Gene Amplification/*physiology
MH  - Humans
MH  - In Situ Hybridization, Fluorescence
MH  - Mice
MH  - Neoplasm Invasiveness
MH  - Oncogenes
MH  - Pancreatic Neoplasms/*genetics/*pathology
MH  - Ubiquitin-Protein Ligases/*genetics
PMC - PMC3161761
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2011/09/03 06:00
MHDA- 2012/03/01 06:00
PMCR- 2011/08/22
CRDT- 2011/09/03 06:00
PHST- 2010/12/14 00:00 [received]
PHST- 2011/08/01 00:00 [accepted]
PHST- 2011/09/03 06:00 [entrez]
PHST- 2011/09/03 06:00 [pubmed]
PHST- 2012/03/01 06:00 [medline]
PHST- 2011/08/22 00:00 [pmc-release]
AID - PONE-D-10-06550 [pii]
AID - 10.1371/journal.pone.0023924 [doi]
PST - ppublish
SO  - PLoS One. 2011;6(8):e23924. doi: 10.1371/journal.pone.0023924. Epub 2011 Aug 22.