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Abrogation of B-RafV600E induced senescence by FoxM1 expression
- Source :
- Biochemical and Biophysical Research Communications. 516:866-871
- Publication Year :
- 2019
- Publisher :
- Elsevier BV, 2019.
-
Abstract
- B-RafV600E oncogene mutation occurs in various cancers and is associated with tumor initiation. However, genetic modification of B-RafV600E in cells induces MAPK activation and results in oncogene-induced senescence. Overcoming the oncogene-induced senescence by B-RafV600E 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-RafV600E and AKT signaling. B-RafV600E 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-RafV600E and FoxM1 overcame the cellular senescence. These observations suggested that FoxM1 is critical downstream gene of AKT and functions to overcome B-RafV600E-induced senescence.
- Subjects :
- 0301 basic medicine
Senescence
Mutation
Oncogene
biology
Chemistry
Biophysics
Cell Biology
Tumor initiation
medicine.disease_cause
Biochemistry
Cell biology
03 medical and health sciences
030104 developmental biology
0302 clinical medicine
Downregulation and upregulation
030220 oncology & carcinogenesis
FOXM1
biology.protein
medicine
PTEN
Molecular Biology
Protein kinase B
Subjects
Details
- ISSN :
- 0006291X
- Volume :
- 516
- Database :
- OpenAIRE
- Journal :
- Biochemical and Biophysical Research Communications
- Accession number :
- edsair.doi...........0df9ca11398d637cb8710f6f947442d0