Targeting Akt3 Signaling in Triple Negative Breast Cancer.

Cancer Research

PubMedID: 24335962

Chin YR, Yoshida T, Marusyk A, Beck AH, Polyak K, Toker A. Targeting Akt3 Signaling in Triple Negative Breast Cancer. Cancer Res. 2014;74(3):964-73.
Triple negative breast cancer (TNBC) is currently the only major breast tumor subtype without effective targeted therapy and as a consequence in general has poor outcome. To identify new therapeutic targets in TNBC we performed an shRNA screen for protein kinases commonly amplified and overexpressed in breast cancer. Using this approach, we identified AKT3 as a gene preferentially required for the growth of TNBCs. Downregulation of Akt3 significantly inhibits the growth of TNBC lines in 3D spheroid cultures and in mouse xenograft models whereas loss of Akt1 or Akt2 have more modest effects. Akt3 silencing markedly upregulates the p27 cell cycle inhibitor and this is critical for the ability of Akt3 to inhibit spheroid growth. In contrast to Akt1, Akt3 silencing results in only a minor enhancement of migration and does not promote invasion. Depletion of Akt3 in TNBC sensitizes cells to the pan-Akt inhibitor GSK690693. These results imply that Akt3 has a specific function in TNBCs, thus, its therapeutic targeting may provide a new treatment option for this tumor subtype.