A functional genetic screen defines the AKT-induced senescence signaling network

Keefe T Chan; Shaun Blake; Haoran Zhu; Jian Kang; Anna S Trigos; Piyush B Madhamshettiwar; Jeannine Diesch; Lassi Paavolainen; Peter Horvath; Ross D Hannan; Amee J George; Elaine Sanij; Katherine M Hannan; Kaylene J Simpson; Richard B Pearson

Journal article

A functional genetic screen defines the AKT-induced senescence signaling network

Keefe T Chan, Shaun Blake, Haoran Zhu, Jian Kang, Anna S Trigos, Piyush B Madhamshettiwar, Jeannine Diesch, Lassi Paavolainen, Peter Horvath, Ross D Hannan, Amee J George, Elaine Sanij, Katherine M Hannan, Kaylene J Simpson, Richard B Pearson

Cell Death and Differentiation | Springer Nature | Published : 2020

DOI: 10.1038/s41418-019-0384-8

Abstract

Exquisite regulation of PI3K/AKT/mTORC1 signaling is essential for homeostatic control of cell growth, proliferation, and survival. Aberrant activation of this signaling network is an early driver of many sporadic human cancers. Paradoxically, sustained hyperactivation of the PI3K/AKT/mTORC1 pathway in nontransformed cells results in cellular senescence, which is a tumor-suppressive mechanism that must be overcome to promote malignant transformation. While oncogene-induced senescence (OIS) driven by excessive RAS/ERK signaling has been well studied, little is known about the mechanisms underpinning the AKT-induced senescence (AIS) response. Here, we utilize a combination of transcriptome and..

View full abstract