Sustained overexpression of Redd1 leads to Akt activation involved in cell survival

• The stable expression of Redd1 triggers Akt phosphorylation.
• Redd1-induced Akt activation is at least partly mediated by mTORC1.
• Dual inhibition of mTORC1/2 enhances cisplatin sensitivity, in cells in which Akt is activated by mTORC1 inhibition.

Herein, we show that the constitutive overexpression of Redd1, a negative regulator of mTORC1, induces Akt activation in lung cancer cells. Akt phosphorylation was reduced to basal levels by Rictor siRNA, suggesting the involvement of mTORC2 in this process. Perifosine and PP242, selective inhibitors of Akt and mTORC1/2, respectively, efficiently suppressed the Akt phosphorylation that was induced by the sustained overexpression of Redd1 and increased the sensitivity of the cells to cisplatin. Therefore, the sustained overexpression of Redd1 leads to mTORC1 inhibition and to consequent Akt activation that is involved in cell survival. This finding highlights the importance of Akt activation as a therapeutic target to overcome resistance to chemotherapy.