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Publication : AKT1 Activation Promotes Development of Melanoma Metastases.

First Author  Cho JH Year  2015
Journal  Cell Rep Volume  13
Issue  5 Pages  898-905
PubMed ID  26565903 Mgi Jnum  J:228953
Mgi Id  MGI:5749892 Doi  10.1016/j.celrep.2015.09.057
Citation  Cho JH, et al. (2015) AKT1 Activation Promotes Development of Melanoma Metastases. Cell Rep 13(5):898-905
abstractText  Metastases are the major cause of melanoma-related mortality. Previous studies implicating aberrant AKT signaling in human melanoma metastases led us to evaluate the effect of activated AKT1 expression in non-metastatic BRAF(V600E)/Cdkn2a(Null) mouse melanomas in vivo. Expression of activated AKT1 resulted in highly metastatic melanomas with lung and brain metastases in 67% and 17% of our mice, respectively. Silencing of PTEN in BRAF(V600E)/Cdkn2a(Null) melanomas cooperated with activated AKT1, resulting in decreased tumor latency and the development of lung and brain metastases in nearly 80% of tumor-bearing mice. These data demonstrate that AKT1 activation is sufficient to elicit lung and brain metastases in this context and reveal that activation of AKT1 is distinct from PTEN silencing in metastatic melanoma progression. These findings advance our knowledge of the mechanisms driving melanoma metastasis and may provide valuable insights for clinical management of this disease.
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