PMID- 30300142
OWN - NLM
STAT- MEDLINE
DCOM- 20190916
LR  - 20220129
IS  - 1558-8238 (Electronic)
IS  - 0021-9738 (Print)
IS  - 0021-9738 (Linking)
VI  - 128
IP  - 12
DP  - 2018 Dec 3
TI  - Temporal dynamics of Wnt-dependent transcriptome reveal an oncogenic 
      Wnt/MYC/ribosome axis.
PG  - 5620-5633
LID - 122383 [pii]
LID - 10.1172/JCI122383 [doi]
AB  - Activating mutations in the Wnt pathway drive a variety of cancers, but the 
      specific targets and pathways activated by Wnt ligands are not fully understood. 
      To bridge this knowledge gap, we performed a comprehensive time-course analysis 
      of Wnt-dependent signaling pathways in an orthotopic model of Wnt-addicted 
      pancreatic cancer, using a porcupine (PORCN) inhibitor currently in clinical 
      trials, and validated key results in additional Wnt-addicted models. The temporal 
      analysis of the drug-perturbed transcriptome demonstrated direct and indirect 
      regulation of more than 3,500 Wnt-activated genes (23% of the transcriptome). 
      Regulation was both via Wnt/beta-catenin and through the modulation of protein 
      abundance of important transcription factors, including MYC, via Wnt-dependent 
      stabilization of proteins (Wnt/STOP). Our study identifies a central role of 
      Wnt/beta-catenin and Wnt/STOP signaling in controlling ribosome biogenesis, a key 
      driver of cancer proliferation.
FAU - Madan, Babita
AU  - Madan B
AD  - Programme in Cancer and Stem Cell Biology, Duke-NUS Medical School, Singapore.
FAU - Harmston, Nathan
AU  - Harmston N
AD  - Programme in Cancer and Stem Cell Biology, Duke-NUS Medical School, Singapore.
AD  - Centre for Computational Biology and Programme in Cardiovascular and Metabolic 
      Disorders, Duke-NUS Medical School, Singapore.
FAU - Nallan, Gahyathiri
AU  - Nallan G
AD  - Programme in Cancer and Stem Cell Biology, Duke-NUS Medical School, Singapore.
FAU - Montoya, Alex
AU  - Montoya A
AD  - MRC London Institute of Medical Sciences, Imperial College London, Hammersmith 
      Campus, London, United Kingdom.
FAU - Faull, Peter
AU  - Faull P
AD  - MRC London Institute of Medical Sciences, Imperial College London, Hammersmith 
      Campus, London, United Kingdom.
FAU - Petretto, Enrico
AU  - Petretto E
AD  - Centre for Computational Biology and Programme in Cardiovascular and Metabolic 
      Disorders, Duke-NUS Medical School, Singapore.
AD  - MRC London Institute of Medical Sciences, Imperial College London, Hammersmith 
      Campus, London, United Kingdom.
FAU - Virshup, David M
AU  - Virshup DM
AD  - Programme in Cancer and Stem Cell Biology, Duke-NUS Medical School, Singapore.
AD  - Department of Pediatrics, Duke University School of Medicine, Durham, North 
      Carolina, USA.
LA  - eng
GR  - MC_U120097112/MRC_/Medical Research Council/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20181112
PL  - United States
TA  - J Clin Invest
JT  - The Journal of clinical investigation
JID - 7802877
RN  - 0 (MYC protein, human)
RN  - 0 (Membrane Proteins)
RN  - 0 (Proto-Oncogene Proteins c-myc)
RN  - EC 2.3.- (Acyltransferases)
RN  - EC 2.3.1.- (PORCN protein, human)
SB  - IM
MH  - Acyltransferases/antagonists & inhibitors/genetics/metabolism
MH  - Animals
MH  - Cell Line, Tumor
MH  - Membrane Proteins/antagonists & inhibitors/genetics/metabolism
MH  - Mice
MH  - Mice, Inbred NOD
MH  - Mice, SCID
MH  - Neoplasms, Experimental/drug therapy/genetics/*metabolism/pathology
MH  - Pancreatic Neoplasms/drug therapy/genetics/*metabolism/pathology
MH  - Protein Stability
MH  - Proto-Oncogene Proteins c-myc/genetics/*metabolism
MH  - Ribosomes/genetics/*metabolism/pathology
MH  - *Transcriptome
MH  - *Wnt Signaling Pathway
PMC - PMC6264740
OTO - NOTNLM
OT  - Cancer
OT  - Cell Biology
OT  - Mouse models
OT  - Oncogenes
OT  - Oncology
COIS- Conflict of interest: BM and DMV have a financial interest in ETC-159 (patent 
      WO2014/175832).
EDAT- 2018/10/10 06:00
MHDA- 2019/09/17 06:00
PMCR- 2019/03/03
CRDT- 2018/10/10 06:00
PHST- 2018/05/22 00:00 [received]
PHST- 2018/10/02 00:00 [accepted]
PHST- 2018/10/10 06:00 [pubmed]
PHST- 2019/09/17 06:00 [medline]
PHST- 2018/10/10 06:00 [entrez]
PHST- 2019/03/03 00:00 [pmc-release]
AID - 122383 [pii]
AID - 10.1172/JCI122383 [doi]
PST - ppublish
SO  - J Clin Invest. 2018 Dec 3;128(12):5620-5633. doi: 10.1172/JCI122383. Epub 2018 
      Nov 12.