AKT1 Activation Promotes Development of Melanoma Metastases

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. [Display omitted] •Expression of activated AKT1 promotes melanoma formation and metastasis•Loss of Pten cooperates with AKT1 activation to promote melanoma metastasis•mTOR signaling downstream of AKT1 is implicated in driving metastasis AKT signaling has been implicated in melanoma metastasis; however, the ability of activated AKT1 to promote melanoma metastasis in vivo has not been explored. Cho et al. show that expression of activated AKT1 in BRAFV600E/Cdkn2aNull melanomas is sufficient to promote tumor cell dissemination to the lungs and brain.