AKT1 Activation Promotes Development of Melanoma Metastases

Joseph H. Cho, James P. Robinson, Rowan A. Arave, William J. Burnett, David A. Kircher, Guo Chen, Michael A. Davies, Allie H. Grossmann, Matthew W. VanBrocklin, Martin McMahon, Sheri L. Holmen

Research output: Contribution to journalArticlepeer-review

105 Scopus citations


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 BRAFV600E/Cdkn2aNull 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 BRAFV600E/Cdkn2aNull 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.

Original languageEnglish (US)
Pages (from-to)898-905
Number of pages8
JournalCell reports
Issue number5
StatePublished - Nov 3 2015

Bibliographical note

Publisher Copyright:
© 2015 The Authors.


Dive into the research topics of 'AKT1 Activation Promotes Development of Melanoma Metastases'. Together they form a unique fingerprint.

Cite this