PMID- 22509316
OWN - NLM
STAT- MEDLINE
DCOM- 20120820
LR  - 20231105
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 7
IP  - 4
DP  - 2012
TI  - PORCN moonlights in a Wnt-independent pathway that regulates cancer cell 
      proliferation.
PG  - e34532
LID - 10.1371/journal.pone.0034532 [doi]
LID - e34532
AB  - Porcupine (PORCN) is a membrane-bound O-acyl transferase that is required for the 
      palmitoylation of Wnt proteins, and that is essential in diverse Wnt pathways for 
      Wnt-Wntless (WLS) binding, Wnt secretion, and Wnt signaling activity. We tested 
      if PORCN was required for the proliferation of transformed cells. Knockdown of 
      PORCN by multiple independent siRNAs results in a cell growth defect in a subset 
      of epithelial cancer cell lines. The growth defect is transformation-dependent in 
      human mammary epithelial (HMEC) cells. Additionally, inducible PORCN knockdown by 
      two independent shRNAs markedly reduces the growth of established MDA-MB-231 
      cancers in orthotopic xenografts in immunodeficient mice. Unexpectedly, the 
      proliferation defect resulting from loss of PORCN occurs in a Wnt-independent 
      manner, as it is rescued by re-expression of catalytically inactive PORCN, and is 
      not seen after RNAi-mediated knockdown of the Wnt carrier protein WLS, nor after 
      treatment with the PORCN inhibitor IWP. Consistent with a role in a 
      Wnt-independent pathway, knockdown of PORCN regulates a distinct set of genes 
      that are not altered by other inhibitors of Wnt signaling. PORCN protein thus 
      appears to moonlight in a novel signaling pathway that is rate-limiting for 
      cancer cell growth and tumorigenesis independent of its enzymatic function in Wnt 
      biosynthesis and secretion.
FAU - Covey, Tracy M
AU  - Covey TM
AD  - Cancer and Stem Cell Biology, Duke-NUS Graduate Medical School, Singapore, 
      Singapore.
FAU - Kaur, Simran
AU  - Kaur S
FAU - Tan Ong, Tina
AU  - Tan Ong T
FAU - Proffitt, Kyle D
AU  - Proffitt KD
FAU - Wu, Yonghui
AU  - Wu Y
FAU - Tan, Patrick
AU  - Tan P
FAU - Virshup, David M
AU  - Virshup DM
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120411
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Gpr177 protein, mouse)
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (Membrane Proteins)
RN  - 0 (Receptors, G-Protein-Coupled)
RN  - 0 (Wnt Proteins)
RN  - EC 2.3.- (Acyltransferases)
RN  - EC 2.3.1.- (PORCN protein, human)
SB  - IM
MH  - Acyltransferases
MH  - Animals
MH  - Breast Neoplasms/genetics/*pathology
MH  - Cell Line, Tumor
MH  - Cell Proliferation
MH  - Cell Transformation, Neoplastic
MH  - Female
MH  - Gene Knockdown Techniques
MH  - Humans
MH  - Intracellular Signaling Peptides and Proteins/deficiency/genetics
MH  - Membrane Proteins/deficiency/genetics/*metabolism
MH  - Mice
MH  - Mutation
MH  - Neoplasms, Glandular and Epithelial/genetics/*pathology
MH  - Receptors, G-Protein-Coupled
MH  - *Signal Transduction/genetics
MH  - Wnt Proteins/*metabolism
PMC - PMC3324524
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2012/04/18 06:00
MHDA- 2012/08/21 06:00
PMCR- 2012/04/11
CRDT- 2012/04/18 06:00
PHST- 2011/12/08 00:00 [received]
PHST- 2012/03/01 00:00 [accepted]
PHST- 2012/04/18 06:00 [entrez]
PHST- 2012/04/18 06:00 [pubmed]
PHST- 2012/08/21 06:00 [medline]
PHST- 2012/04/11 00:00 [pmc-release]
AID - PONE-D-11-24577 [pii]
AID - 10.1371/journal.pone.0034532 [doi]
PST - ppublish
SO  - PLoS One. 2012;7(4):e34532. doi: 10.1371/journal.pone.0034532. Epub 2012 Apr 11.