PMID- 21277992
OWN - NLM
STAT- MEDLINE
DCOM- 20110603
LR  - 20110228
IS  - 1878-5875 (Electronic)
IS  - 1357-2725 (Linking)
VI  - 43
IP  - 4
DP  - 2011 Apr
TI  - Neural cell adhesion molecule potentiates invasion and metastasis of melanoma 
      cells through CAMP-dependent protein kinase and phosphatidylinositol 3-kinase 
      pathways.
PG  - 682-90
LID - 10.1016/j.biocel.2011.01.016 [doi]
AB  - Neural cell adhesion molecule (NCAM) has been implicated in tumor metastasis yet 
      its function in melanoma progression remains unclear. Here, we demonstrate that 
      stably silencing NCAM expression in mouse melanoma B16F0 cells perturbs their 
      cellular invasion and metastatic dissemination in vivo. The pro-invasive function 
      of NCAM is exerted via dual mechanisms involving both cAMP-dependent protein 
      kinase (PKA) and phosphatidylinositol 3-kinase (PI3K) pathways. Pharmacologic 
      inhibition of PKA and PI3K leads to impaired cellular invasion. In contrast, 
      forced expression of constitutively activated Akt, the major downstream target of 
      PI3K, restores the defective cellular invasiveness of NCAM knock-down (KD) B16F0 
      cells. Furthermore, attenuation of either PKA or Akt activity in NCAM KD cells is 
      shown to affect their common downstream target, transcription factor cAMP 
      response element binding protein (CREB), which in turn down-regulates mRNA 
      expression of matrix metalloproteinase-2 (MMP-2), thus contributes to impaired 
      cellular invasion and metastasis of melanoma cells. Together, these findings 
      indicate that NCAM potentiates cellular invasion and metastasis of melanoma cells 
      through stimulation of PKA and PI3K signaling pathways thus suggesting the 
      potential implication of anti-NCAM strategy in melanoma treatment.
CI  - Copyright (c) 2011 Elsevier Ltd. All rights reserved.
FAU - Shi, Yu
AU  - Shi Y
AD  - School of Biological Sciences, Nanyang Technological University, #60 Nanyang 
      Drive, Singapore 637551, Singapore.
FAU - Liu, Rui
AU  - Liu R
FAU - Zhang, Si
AU  - Zhang S
FAU - Xia, Yin-Yan
AU  - Xia YY
FAU - Yang, Hai-Jie
AU  - Yang HJ
FAU - Guo, Ke
AU  - Guo K
FAU - Zeng, Qi
AU  - Zeng Q
FAU - Feng, Zhi-Wei
AU  - Feng ZW
LA  - eng
PT  - Journal Article
DEP - 20110126
PL  - Netherlands
TA  - Int J Biochem Cell Biol
JT  - The international journal of biochemistry & cell biology
JID - 9508482
RN  - 0 (Cyclic AMP Response Element-Binding Protein)
RN  - 0 (Neural Cell Adhesion Molecules)
RN  - EC 2.7.1.137 (Phosphatidylinositol 3-Kinase)
RN  - EC 2.7.11.11 (Cyclic AMP-Dependent Protein Kinases)
RN  - EC 3.4.24.24 (Matrix Metalloproteinase 2)
SB  - IM
MH  - Animals
MH  - Cell Line, Tumor
MH  - Cell Movement
MH  - Cyclic AMP Response Element-Binding Protein/metabolism
MH  - Cyclic AMP-Dependent Protein Kinases/*metabolism
MH  - Disease Progression
MH  - Down-Regulation
MH  - Enzyme Activation
MH  - Gene Expression Regulation, Neoplastic
MH  - Gene Knockdown Techniques
MH  - Gene Silencing
MH  - Matrix Metalloproteinase 2/genetics
MH  - Melanoma, Experimental/genetics/*pathology
MH  - Mice
MH  - Neoplasm Invasiveness
MH  - Neoplasm Metastasis
MH  - Neural Cell Adhesion Molecules/deficiency/genetics/*metabolism
MH  - Phosphatidylinositol 3-Kinase/*metabolism
MH  - Phosphorylation
MH  - *Signal Transduction
EDAT- 2011/02/01 06:00
MHDA- 2011/06/04 06:00
CRDT- 2011/02/01 06:00
PHST- 2010/11/27 00:00 [received]
PHST- 2011/01/18 00:00 [revised]
PHST- 2011/01/19 00:00 [accepted]
PHST- 2011/02/01 06:00 [entrez]
PHST- 2011/02/01 06:00 [pubmed]
PHST- 2011/06/04 06:00 [medline]
AID - S1357-2725(11)00033-1 [pii]
AID - 10.1016/j.biocel.2011.01.016 [doi]
PST - ppublish
SO  - Int J Biochem Cell Biol. 2011 Apr;43(4):682-90. doi: 
      10.1016/j.biocel.2011.01.016. Epub 2011 Jan 26.