1. Strategies for differential inhibition of mTORC1 and mTORC2 with rapamycin.
Strategies for differential inhibition of mTORC1 and mTORC2 with rapamycin. Using low-dose rapamycin (left), phosphorylation of S6K by mTORC1 is suppressed, which retards G1 cell-cycle progression (59, 70). Using high-dose rapamycin (middle), both phosphorylation of S6K and 4E-BP1 (38, 50) are suppressed. However, this treatment frequently leads to a feedback activation of Akt phosphorylation by mTORC2 (46, 47), which promotes survival (62). Suppressing PLD activity sensitizes cells to rapamycin, sensitizing mTORC2 to low-dose rapamycin (27, 32), which prevents feedback activation of Akt and leads to apoptosis.
Suman Mukhopadhyay et al. Mol Cancer Ther 2016;15:
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