PMID- 27879264
OWN - NLM
STAT- MEDLINE
DCOM- 20170724
LR  - 20180411
IS  - 1538-7445 (Electronic)
IS  - 0008-5472 (Linking)
VI  - 77
IP  - 3
DP  - 2017 Feb 1
TI  - Differential Regulation of the Melanoma Proteome by eIF4A1 and eIF4E.
PG  - 613-622
LID - 10.1158/0008-5472.CAN-16-1298 [doi]
AB  - Small molecules and antisense oligonucleotides that inhibit the translation
      initiation factors eIF4A1 and eIF4E have been explored as broad-based therapeutic
      agents for cancer treatment, based on the frequent upregulation of these two
      subunits of the eIF4F cap-binding complex in many cancer cells. Here, we provide 
      support for these therapeutic approaches with mechanistic studies of eIF4F-driven
      tumor progression in a preclinical model of melanoma. Silencing eIF4A1 or eIF4E
      decreases melanoma proliferation and invasion. There were common effects on the
      level of cell-cycle proteins that could explain the antiproliferative effects in 
      vitro Using clinical specimens, we correlate the common cell-cycle targets of
      eIF4A1 and eIF4E with patient survival. Finally, comparative proteomic and
      transcriptomic analyses reveal extensive mechanistic divergence in response to
      eIF4A1 or eIF4E silencing. Current models indicate that eIF4A1 and eIF4E function
      together through the 5'UTR to increase translation of oncogenes. In contrast, our
      data demonstrate that the common effects of eIF4A1 and eIF4E on translation are
      mediated by the coding region and 3'UTR. Moreover, their divergent effects occur 
      through the 5'UTR. Overall, our work shows that it will be important to evaluate 
      subunit-specific inhibitors of eIF4F in different disease contexts to fully
      understand their anticancer actions. Cancer Res; 77(3); 613-22. (c)2016 AACR.
CI  - (c)2016 American Association for Cancer Research.
FAU - Joyce, Cailin E
AU  - Joyce CE
AD  - Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute,
      Boston, Massachusetts.
AD  - Department of Medicine, Harvard Medical School, Boston, Massachusetts.
AD  - Broad Institute of Harvard and MIT, Cambridge, Massachusetts.
FAU - Yanez, Adrienne G
AU  - Yanez AG
AD  - Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute,
      Boston, Massachusetts.
AD  - Department of Medicine, Harvard Medical School, Boston, Massachusetts.
AD  - Broad Institute of Harvard and MIT, Cambridge, Massachusetts.
FAU - Mori, Akihiro
AU  - Mori A
AD  - Program in Systems Biology and Program in Molecular Medicine, University of
      Massachusetts, Worcester, Massachusetts.
AD  - Onami team, The Systems Biology Institute, Tokyo, Japan.
AD  - Laboratory for Developmental Dynamics, RIKEN Quantitative Biology Center, Hyogo, 
      Japan.
FAU - Yoda, Akinori
AU  - Yoda A
AD  - Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute,
      Boston, Massachusetts.
AD  - Department of Medicine, Harvard Medical School, Boston, Massachusetts.
AD  - Broad Institute of Harvard and MIT, Cambridge, Massachusetts.
FAU - Carroll, Johanna S
AU  - Carroll JS
AD  - Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute,
      Boston, Massachusetts.
AD  - Department of Medicine, Harvard Medical School, Boston, Massachusetts.
AD  - Broad Institute of Harvard and MIT, Cambridge, Massachusetts.
FAU - Novina, Carl D
AU  - Novina CD
AD  - Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute,
      Boston, Massachusetts. carl_novina@dfci.harvard.edu.
AD  - Department of Medicine, Harvard Medical School, Boston, Massachusetts.
AD  - Broad Institute of Harvard and MIT, Cambridge, Massachusetts.
LA  - eng
GR  - R01 CA140986/CA/NCI NIH HHS/United States
GR  - T32 CA070083/CA/NCI NIH HHS/United States
GR  - F32 HL124941/HL/NHLBI NIH HHS/United States
GR  - T32 GM007266/GM/NIGMS NIH HHS/United States
GR  - F31 GM087947/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20161122
PL  - United States
TA  - Cancer Res
JT  - Cancer research
JID - 2984705R
RN  - 0 (Eukaryotic Initiation Factor-4E)
RN  - 0 (Eukaryotic Initiation Factor-4F)
RN  - 0 (Proteome)
SB  - IM
EIN - Cancer Res. 2017 Mar 15;77(6):1505. PMID: 28298386
MH  - Cell Line, Tumor
MH  - Eukaryotic Initiation Factor-4E/*metabolism
MH  - Eukaryotic Initiation Factor-4F/*metabolism
MH  - Gene Knockdown Techniques
MH  - Gene Regulatory Networks
MH  - Humans
MH  - Mass Spectrometry
MH  - Melanoma/*metabolism/pathology
MH  - Proteome
MH  - Proteomics
MH  - Skin Neoplasms/*metabolism/pathology
PMC - PMC5362820
MID - NIHMS832368
EDAT- 2016/11/24 06:00
MHDA- 2017/07/25 06:00
CRDT- 2016/11/24 06:00
PHST- 2016/05/06 00:00 [received]
PHST- 2016/11/16 00:00 [revised]
PHST- 2016/11/16 00:00 [accepted]
PHST- 2016/11/24 06:00 [pubmed]
PHST- 2017/07/25 06:00 [medline]
PHST- 2016/11/24 06:00 [entrez]
AID - 0008-5472.CAN-16-1298 [pii]
AID - 10.1158/0008-5472.CAN-16-1298 [doi]
PST - ppublish
SO  - Cancer Res. 2017 Feb 1;77(3):613-622. doi: 10.1158/0008-5472.CAN-16-1298. Epub
      2016 Nov 22.