PMID- 25562667
OWN - NLM
STAT- MEDLINE
DCOM- 20150720
LR  - 20181113
IS  - 1523-1747 (Electronic)
IS  - 0022-202X (Linking)
VI  - 135
IP  - 5
DP  - 2015 May
TI  - eIF4E is an adverse prognostic marker of melanoma patient survival by increasing 
      melanoma cell invasion.
PG  - 1358-1367
LID - S0022-202X(15)37255-9 [pii]
LID - 10.1038/jid.2014.552 [doi]
AB  - Human cutaneous melanoma is a devastating skin cancer because of its invasive 
      nature and high metastatic potential. We used tissue microarray to study the role 
      of human eukaryotic translation initiation factor 4E (eIF4E) in melanoma 
      progression in 448 melanocytic lesions and found that high eIF4E expression was 
      significantly increased in primary melanomas compared with dysplastic nevi 
      (P<0.001), and further increased in metastatic melanomas (P<0.001). High eIF4E 
      expression was associated with melanoma thickness (P=0.046), and poor overall and 
      disease-specific 5-year survival of all, and primary melanoma patients, 
      especially those with tumors >/=1 mm thick. Multivariate Cox regression analysis 
      revealed that eIF4E is an independent prognostic marker. eIF4E knockdown (KD) in 
      melanoma cells resulted in a significant increase in apoptosis (sub-G1 
      populations) and decrease in cell proliferation, and also resulted in 
      downregulation of mesenchymal markers and upregulation of E-cadherin. In 
      addition, eIF4E KD led to a decrease in melanoma cell invasion, matrix 
      metalloproteinase-2 expression and activity, c-myc and BCL2 expression, and an 
      increase in cleaved PARP and cleaved caspase-3 expression and chemosensitivity. 
      Taken together, our data suggest that the eIF4E may promote melanoma cell 
      invasion and metastasis, and may also serve as a promising prognostic marker and 
      a potential therapeutic target for melanoma.
FAU - Khosravi, Shahram
AU  - Khosravi S
AD  - Department of Dermatology and Skin Science, Vancouver Coastal Health Research 
      Institute, University of British Columbia, Vancouver, British Columbia, Canada; 
      Department of Surgery, Vancouver Coastal Health Research Institute, University of 
      British Columbia, Vancouver, British Columbia, Canada. Electronic address: 
      shahramk1@yahoo.com.
FAU - Tam, Kevin J
AU  - Tam KJ
AD  - Department of Surgery, Vancouver Coastal Health Research Institute, University of 
      British Columbia, Vancouver, British Columbia, Canada.
FAU - Ardekani, Gholamreza S
AU  - Ardekani GS
AD  - Department of Dermatology and Skin Science, Vancouver Coastal Health Research 
      Institute, University of British Columbia, Vancouver, British Columbia, Canada.
FAU - Martinka, Magdalena
AU  - Martinka M
AD  - Department of Pathology, Vancouver Coastal Health Research Institute, University 
      of British Columbia, Vancouver, British Columbia, Canada.
FAU - McElwee, Kevin J
AU  - McElwee KJ
AD  - Department of Dermatology and Skin Science, Vancouver Coastal Health Research 
      Institute, University of British Columbia, Vancouver, British Columbia, Canada.
FAU - Ong, Christopher J
AU  - Ong CJ
AD  - Department of Surgery, Vancouver Coastal Health Research Institute, University of 
      British Columbia, Vancouver, British Columbia, Canada.
LA  - eng
GR  - MOP-110974/Canadian Institutes of Health Research/Canada
GR  - MOP-93810/Canadian Institutes of Health Research/Canada
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150106
PL  - United States
TA  - J Invest Dermatol
JT  - The Journal of investigative dermatology
JID - 0426720
RN  - 0 (Biomarkers, Tumor)
RN  - 0 (Eukaryotic Initiation Factor-4E)
SB  - IM
MH  - Apoptosis/physiology
MH  - Biomarkers, Tumor/*metabolism
MH  - Cell Line, Tumor
MH  - Cell Movement/physiology
MH  - Cell Proliferation/physiology
MH  - Disease Progression
MH  - Eukaryotic Initiation Factor-4E/*metabolism
MH  - Female
MH  - Humans
MH  - Kaplan-Meier Estimate
MH  - Male
MH  - Melanoma/metabolism/*mortality/*pathology
MH  - Middle Aged
MH  - Neoplasm Invasiveness
MH  - Prognosis
MH  - Regression Analysis
MH  - Skin Neoplasms/metabolism/*mortality/*pathology
MH  - Survival Rate
EDAT- 2015/01/07 06:00
MHDA- 2015/07/21 06:00
CRDT- 2015/01/07 06:00
PHST- 2014/08/11 00:00 [received]
PHST- 2014/12/01 00:00 [revised]
PHST- 2014/12/11 00:00 [accepted]
PHST- 2015/01/07 06:00 [entrez]
PHST- 2015/01/07 06:00 [pubmed]
PHST- 2015/07/21 06:00 [medline]
AID - S0022-202X(15)37255-9 [pii]
AID - 10.1038/jid.2014.552 [doi]
PST - ppublish
SO  - J Invest Dermatol. 2015 May;135(5):1358-1367. doi: 10.1038/jid.2014.552. Epub 
      2015 Jan 6.