Open access
Dysregulated AKT signaling reprograms osteosarcoma to drive selective reliance on EP300
Ian M. Delahunty
S. Nance
Yang Zhang
François Lamoureux
Qi Liu
W. C. Wright
K. Ritter
Noha A. M. Shendy
Bénédicte Brounais-Le Roye
Sandra J. Kietlinska
M. A. Mohammad Nezhady
Yuan Feng
B. De Kegel
M. Rees
Mustafa Kocak
Ashish B. George
Mei-Fen Lu
A. Kavirayani
Bo Wang
Yan-Ling Liu
P. Prinsen
Yousef Khashana
V. Ebegboni
Melissa M. Ronan
Jennifer A. Roth
E. Sweet-Cordero
Lillian M. Guenther
P. Geeleher
Xiao-Tu Ma
B. Ory
Jun Qi
Brian J. Abraham
A. Durbin
Medicine
Abstract
Here, Delahunty et al. identify that EP300 controls the growth of AKT-dysregulated osteosarcoma cells by regulating expression of state-specific genetic dependencies. AKT inhibitors synergize with EP300 degraders to suppress osteosarcoma growth in vitro and in vivo. These agents positively combine across cancer cells in a manner dependent on control of protein synthesis.