Biochemical and Biophysical Research Communications, Vol.516, No.3, 866-871, 2019
Abrogation of B-Raf(V600E) induced senescence by FoxM1 expression
B-Raf(V600E) oncogene mutation occurs in various cancers and is associated with tumor initiation. However, genetic modification of B-Raf(V600E) in cells induces MAPK activation and results in oncogene-induced senescence. Overcoming the oncogene-induced senescence by B-Raf(V600E) requires activation of another oncogene pathway, such as AICT signaling. In the present study, we explored the factors involved in overcoming the senescence program in cells activated by B-Rafv6 E and ART signaling. B-Raf(V600E) activation caused a feedback inhibition of AKT phosphorylation and resulted in downregulation of FoxMl, one of the AKT downstream components. AKT activation by PTEN downregulation induced FoxMl expression, and co-expression of B-Raf(V600E) and FoxMl overcame the cellular senescence. These observations suggested that FoxMl is critical downstream gene of AKT and functions to overcome B-Raf(V600E)-induced senescence. (C) 2019 Elsevier Inc. All rights reserved.