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Cell Rep. 2015 Nov 3;13(5):898-905. doi: 10.1016/j.celrep.2015.09.057. Epub 2015 Oct 22.

AKT1 Activation Promotes Development of Melanoma Metastases.

Author information

1
Department of Oncological Sciences, University of Utah Health Sciences Center, Salt Lake City, UT 84112, USA.
2
Hormel Institute, University of Minnesota, Austin, MN 55912, USA.
3
Department of Chemistry, University of Utah Health Sciences Center, Salt Lake City, UT 84112, USA.
4
Department of Melanoma Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
5
Department of Pathology, University of Utah Health Sciences Center, Salt Lake City, UT 84112, USA.
6
Department of Oncological Sciences, University of Utah Health Sciences Center, Salt Lake City, UT 84112, USA; Department of Surgery, University of Utah Health Sciences Center, Salt Lake City, UT 84112, USA; Huntsman Cancer Institute, University of Utah Health Sciences Center, Salt Lake City, UT 84112, USA.
7
Department of Oncological Sciences, University of Utah Health Sciences Center, Salt Lake City, UT 84112, USA; Huntsman Cancer Institute, University of Utah Health Sciences Center, Salt Lake City, UT 84112, USA; Department of Dermatology, University of Utah Health Sciences Center, Salt Lake City, UT 84112, USA.
8
Department of Oncological Sciences, University of Utah Health Sciences Center, Salt Lake City, UT 84112, USA; Department of Surgery, University of Utah Health Sciences Center, Salt Lake City, UT 84112, USA; Huntsman Cancer Institute, University of Utah Health Sciences Center, Salt Lake City, UT 84112, USA. Electronic address: sheri.holmen@hci.utah.edu.

Abstract

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.

PMID:
26565903
PMCID:
PMC4646731
DOI:
10.1016/j.celrep.2015.09.057
[Indexed for MEDLINE]
Free PMC Article

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