AKT inhibition relieves feedback suppression of receptor tyrosine kinase expression and activity.

@article{Chandarlapaty2011AKTIR,
  title={AKT inhibition relieves feedback suppression of receptor tyrosine kinase expression and activity.},
  author={Sarat Chandarlapaty and Ayana Sawai and Maurizio Scaltriti and Vanessa S. Rodrik-Outmezguine and Olivera Grbovic-Huezo and Violeta Serra and Pradip K. Majumder and Jos{\'e} Baselga and Neal Rosen},
  journal={Cancer cell},
  year={2011},
  volume={19 1},
  pages={58-71}
}
Activation of the PI3K-AKT pathway in tumors is modulated by negative feedback, including mTORC1-mediated inhibition of upstream signaling. We now show that AKT inhibition induces the expression and phosphorylation of multiple receptor tyrosine kinases (RTKs). In a wide spectrum of tumor types, inhibition of AKT induces a conserved set of RTKs, including HER3, IGF-1R, and insulin receptor. This is in part due to mTORC1 inhibition and in part secondary to a FOXO-dependent activation of receptor… CONTINUE READING
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