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Updated: Jan 22, 2026

Techniques to Induce and Quantify Cellular Senescence
06:51

Techniques to Induce and Quantify Cellular Senescence

Published on: May 1, 2017

34.9K

Abrogation of B-RafV600E induced senescence by FoxM1 expression

Yong Won Choi1, Ga Eun Nam2, Young Hwa Kim2

  • 1Department of Hematology-Oncology, Ajou University School of Medicine, Suwon, 443-721, South Korea.

Biochemical and Biophysical Research Communications
|July 5, 2019
PubMed

Insights

The B-RafV600E oncogene mutation can cause cancer, but also senescence. FoxM1, an AKT downstream gene, is key to overcoming this senescence when both B-RafV600E and AKT signaling are activated.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cellular Senescence

Background:

  • The B-RafV600E oncogene mutation is implicated in various cancers and tumor initiation.
  • While B-RafV600E activation triggers MAPK signaling and oncogene-induced senescence, overcoming this requires additional oncogenic pathways like AKT signaling.

Purpose of the Study:

  • To investigate the factors enabling cells to overcome the senescence program induced by combined B-RafV600E and AKT signaling.
  • To elucidate the regulatory relationship between B-RafV600E, AKT, and FoxM1 in the context of cellular senescence.

Main Methods:

  • Investigated the impact of B-RafV600E activation on AKT phosphorylation and FoxM1 expression.
  • Examined the effect of AKT activation, induced by PTEN downregulation, on FoxM1 expression.
  • Assessed the role of co-expressing B-RafV600E and FoxM1 in overcoming cellular senescence.

Main Results:

  • B-RafV600E activation led to feedback inhibition of AKT phosphorylation and downregulation of FoxM1.
  • AKT activation, facilitated by PTEN downregulation, resulted in induced FoxM1 expression.
  • Simultaneous expression of B-RafV600E and FoxM1 successfully overcame B-RafV600E-induced cellular senescence.

Conclusions:

  • FoxM1 acts as a critical downstream gene of AKT signaling.
  • FoxM1 plays a crucial role in overcoming B-RafV600E-induced cellular senescence.
Keywords:
B-RafV600E induced senescenceFoxM1

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