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Abrogation of B-Raf(V600E) induced senescence by FoxM1 expression

Authors
Choi, YW  | Nam, GE | Kim, YH | Yoon, JE | Park, JH | Kim, JH  | Kang, SY  | Park, TJ
Citation
Biochemical and biophysical research communications, 516(3). : 866-871, 2019
Journal Title
Biochemical and biophysical research communications
ISSN
0006-291X1090-2104
Abstract
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 AKT signaling. In the present study, we explored the factors involved in overcoming the senescence program in cells activated by B-Raf(V600E) and AKT signaling. B-Raf(V600E) activation caused a feedback inhibition of AKT phosphorylation and resulted in downregulation of FoxM1, one of the AKT downstream components. AKT activation by PTEN downregulation induced FoxM1 expression, and co-expression of B-Raf(V600E) and FoxM1 overcame the cellular senescence. These observations suggested that FoxM1 is critical downstream gene of AKT and functions to overcome B-Raf(V600E)-induced senescence.
Keywords
MeSH

DOI
10.1016/j.bbrc.2019.06.144
PMID
31270027
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Hematology-Oncology
Journal Papers > School of Medicine / Graduate School of Medicine > Pathology
Journal Papers > School of Medicine / Graduate School of Medicine > Biochemistry & Molecular Biology
Ajou Authors
강, 석윤  |  김, 장희  |  박, 태준  |  최, 용원
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