|
rdf:type |
|
|
lifeskim:mentions |
umls-concept:C0017262,
umls-concept:C0025202,
umls-concept:C0027215,
umls-concept:C0031621,
umls-concept:C0033414,
umls-concept:C0037083,
umls-concept:C0185117,
umls-concept:C0205225,
umls-concept:C0449258,
umls-concept:C0752312,
umls-concept:C1334889,
umls-concept:C1704259,
umls-concept:C1705987,
umls-concept:C1710082,
umls-concept:C2911684
|
|
pubmed:issue |
8
|
|
pubmed:dateCreated |
2006-4-18
|
|
pubmed:abstractText |
Cellular signaling mediated by Notch receptors results in coordinated regulation of cell growth, survival, and differentiation. Aberrant Notch activation has been linked to a variety of human neoplasms. Here, we show that Notch1 signaling drives the vertical growth phase (VGP) of primary melanoma toward a more aggressive phenotype. Constitutive activation of Notch1 by ectopic expression of the Notch1 intracellular domain enables VGP primary melanoma cell lines to proliferate in a serum-independent and growth factor-independent manner in vitro and to grow more aggressively with metastatic activity in vivo. Notch1 activation also enhances tumor cell survival when cultured as three-dimensional spheroids. Such effects of Notch signaling are mediated by activation of the mitogen-activated protein kinase (MAPK) and Akt pathways. Both pathways are activated in melanoma cells following Notch1 pathway activation. Inhibition of either the MAPK or the phosphatidylinositol 3-kinase (PI3K)-Akt pathway reverses the Notch1 signaling-induced tumor cell growth. Moreover, the growth-promoting effect of Notch1 depends on mastermind-like 1. We further showed that Notch1 activation increases tumor cell adhesion and up-regulates N-cadherin expression. Our data show regulation of MAPK/PI3K-Akt pathway activities and expression of N-cadherin by the Notch pathway and provide a mechanistic basis for Notch signaling in the promotion of primary melanoma progression.
|
|
pubmed:grant |
|
|
pubmed:language |
eng
|
|
pubmed:journal |
|
|
pubmed:citationSubset |
IM
|
|
pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD,
http://linkedlifedata.com/resource/pubmed/chemical/CDH2 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Cadherins,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/MAML1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/NOTCH1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Nuclear Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphatidylinositol 3-Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-akt,
http://linkedlifedata.com/resource/pubmed/chemical/Receptor, Notch1,
http://linkedlifedata.com/resource/pubmed/chemical/Trans-Activators,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors
|
|
pubmed:status |
MEDLINE
|
|
pubmed:month |
Apr
|
|
pubmed:issn |
0008-5472
|
|
pubmed:author |
|
|
pubmed:issnType |
Print
|
|
pubmed:day |
15
|
|
pubmed:volume |
66
|
|
pubmed:owner |
NLM
|
|
pubmed:authorsComplete |
Y
|
|
pubmed:pagination |
4182-90
|
|
pubmed:dateRevised |
2010-11-18
|
|
pubmed:meshHeading |
pubmed-meshheading:16618740-Animals,
pubmed-meshheading:16618740-Antigens, CD,
pubmed-meshheading:16618740-Cadherins,
pubmed-meshheading:16618740-Cell Adhesion,
pubmed-meshheading:16618740-Cell Growth Processes,
pubmed-meshheading:16618740-Cell Line, Tumor,
pubmed-meshheading:16618740-DNA-Binding Proteins,
pubmed-meshheading:16618740-Disease Progression,
pubmed-meshheading:16618740-Enzyme Activation,
pubmed-meshheading:16618740-Humans,
pubmed-meshheading:16618740-MAP Kinase Signaling System,
pubmed-meshheading:16618740-Melanoma,
pubmed-meshheading:16618740-Mice,
pubmed-meshheading:16618740-Mice, SCID,
pubmed-meshheading:16618740-Mitogen-Activated Protein Kinases,
pubmed-meshheading:16618740-Nuclear Proteins,
pubmed-meshheading:16618740-Phosphatidylinositol 3-Kinases,
pubmed-meshheading:16618740-Proto-Oncogene Proteins c-akt,
pubmed-meshheading:16618740-Receptor, Notch1,
pubmed-meshheading:16618740-Spheroids, Cellular,
pubmed-meshheading:16618740-Trans-Activators,
pubmed-meshheading:16618740-Transcription Factors,
pubmed-meshheading:16618740-Up-Regulation
|
|
pubmed:year |
2006
|
|
pubmed:articleTitle |
Notch1 signaling promotes primary melanoma progression by activating mitogen-activated protein kinase/phosphatidylinositol 3-kinase-Akt pathways and up-regulating N-cadherin expression.
|
|
pubmed:affiliation |
The Wistar Institute, Philadelphia, Pennsylvania 19104, USA.
|
|
pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
|
