PMID- 21460252
OWN - NLM
STAT- MEDLINE
DCOM- 20110617
LR  - 20211203
IS  - 1091-6490 (Electronic)
IS  - 0027-8424 (Print)
IS  - 0027-8424 (Linking)
VI  - 108
IP  - 16
DP  - 2011 Apr 19
TI  - AMP kinase-related kinase NUAK2 affects tumor growth, migration, and clinical 
      outcome of human melanoma.
PG  - 6597-602
LID - 10.1073/pnas.1007694108 [doi]
AB  - The identification of genes that participate in melanomagenesis should suggest 
      strategies for developing therapeutic modalities. We used a public array 
      comparative genomic hybridization (CGH) database and real-time quantitative PCR 
      (qPCR) analyses to identify the AMP kinase (AMPK)-related kinase NUAK2 as a 
      candidate gene for melanomagenesis, and we analyzed its functions in melanoma 
      cells. Our analyses had identified a locus at 1q32 where genomic gain is strongly 
      associated with tumor thickness, and we used real-time qPCR analyses and 
      regression analyses to identify NUAK2 as a candidate gene at that locus. 
      Associations of relapse-free survival and overall survival of 92 primary melanoma 
      patients with NUAK2 expression measured using immunohistochemistry were 
      investigated using Kaplan-Meier curves, log rank tests, and Cox regression 
      models. Knockdown of NUAK2 induces senescence and reduces S-phase, decreases 
      migration, and down-regulates expression of mammalian target of rapamycin (mTOR). 
      In vivo analysis demonstrated that knockdown of NUAK2 suppresses melanoma tumor 
      growth in mice. Survival analysis showed that the risk of relapse is greater in 
      acral melanoma patients with high levels of NUAK2 expression than in acral 
      melanoma patients with low levels of NUAK2 expression (hazard ratio = 3.88; 95% 
      confidence interval = 1.44-10.50; P = 0.0075). These data demonstrate that NUAK2 
      expression is significantly associated with the oncogenic features of melanoma 
      cells and with the survival of acral melanoma patients. NUAK2 may provide a drug 
      target to suppress melanoma progression. This study further supports the 
      importance of NUAK2 in cancer development and tumor progression, while AMPK has 
      antioncogenic properties.
FAU - Namiki, Takeshi
AU  - Namiki T
AD  - Laboratory of Cell Biology, National Cancer Institute, Bethesda, MD 20814, USA.
FAU - Tanemura, Atsushi
AU  - Tanemura A
FAU - Valencia, Julio C
AU  - Valencia JC
FAU - Coelho, Sergio G
AU  - Coelho SG
FAU - Passeron, Thierry
AU  - Passeron T
FAU - Kawaguchi, Masakazu
AU  - Kawaguchi M
FAU - Vieira, Wilfred D
AU  - Vieira WD
FAU - Ishikawa, Masashi
AU  - Ishikawa M
FAU - Nishijima, Wataru
AU  - Nishijima W
FAU - Izumo, Toshiyuki
AU  - Izumo T
FAU - Kaneko, Yasuhiko
AU  - Kaneko Y
FAU - Katayama, Ichiro
AU  - Katayama I
FAU - Yamaguchi, Yuji
AU  - Yamaguchi Y
FAU - Yin, Lanlan
AU  - Yin L
FAU - Polley, Eric C
AU  - Polley EC
FAU - Liu, Hongfang
AU  - Liu H
FAU - Kawakami, Yutaka
AU  - Kawakami Y
FAU - Eishi, Yoshinobu
AU  - Eishi Y
FAU - Takahashi, Eishi
AU  - Takahashi E
FAU - Yokozeki, Hiroo
AU  - Yokozeki H
FAU - Hearing, Vincent J
AU  - Hearing VJ
LA  - eng
GR  - R01 LM009959/LM/NLM NIH HHS/United States
GR  - ImNIH/Intramural NIH HHS/United States
PT  - Journal Article
PT  - Multicenter Study
PT  - Research Support, N.I.H., Intramural
DEP - 20110401
PL  - United States
TA  - Proc Natl Acad Sci U S A
JT  - Proceedings of the National Academy of Sciences of the United States of America
JID - 7505876
RN  - 0 (Neoplasm Proteins)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (NUAK2 protein, human)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Animals
MH  - *Cell Movement
MH  - Cellular Senescence/genetics
MH  - Disease-Free Survival
MH  - Female
MH  - *Gene Expression Regulation, Enzymologic
MH  - *Gene Expression Regulation, Neoplastic
MH  - Gene Knockdown Techniques
MH  - Genetic Loci/genetics
MH  - Genome-Wide Association Study
MH  - Humans
MH  - Male
MH  - Melanoma/*enzymology/genetics/*mortality/pathology/therapy
MH  - Mice
MH  - Mice, Nude
MH  - Neoplasm Proteins/*biosynthesis/genetics
MH  - Protein Serine-Threonine Kinases/*biosynthesis/genetics
MH  - S Phase/genetics
MH  - Survival Rate
MH  - TOR Serine-Threonine Kinases/genetics/metabolism
PMC - PMC3081019
COIS- The authors declare no conflict of interest.
EDAT- 2011/04/05 06:00
MHDA- 2011/06/18 06:00
PMCR- 2011/10/19
CRDT- 2011/04/05 06:00
PHST- 2011/04/05 06:00 [entrez]
PHST- 2011/04/05 06:00 [pubmed]
PHST- 2011/06/18 06:00 [medline]
PHST- 2011/10/19 00:00 [pmc-release]
AID - 1007694108 [pii]
AID - 201007694 [pii]
AID - 10.1073/pnas.1007694108 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 2011 Apr 19;108(16):6597-602. doi: 
      10.1073/pnas.1007694108. Epub 2011 Apr 1.