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Emerging roles of the p38 MAPK and PI3K/AKT/mTOR pathways in oncogene-induced senescence

Yingxi Xu1, Na Li2, Rong Xiang2

  • 1College of Medicine, Nankai University, 94 Weijin Road, Tianjin, China, 300071; Department of Cell and Molecular Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.

Trends in Biochemical Sciences
|May 14, 2014
PubMed

Insights

Oncogene-induced senescence (OIS) is a crucial tumor-suppressing mechanism. Understanding its intricate signaling network, including key pathways like p38 MAPK and PI3K/AKT/mTOR, can reveal new cancer therapy targets.

Area of Science:

  • Cellular Biology
  • Cancer Research
  • Molecular Oncology

Background:

  • Oncogene-induced senescence (OIS) is a vital tumor-suppressing mechanism that cancer cells must overcome.
  • Activation of tumor suppressor pathways, such as p53/p21(WAF1) and p16(INK4A), is critical for initiating OIS.
  • The DNA damage response, chromatin remodeling, and the senescence-associated secretory phenotype (SASP) play significant roles in OIS initiation and maintenance.

Purpose of the Study:

  • To review recent advancements in understanding the molecular mechanisms underlying OIS.
  • To highlight the roles of specific signaling pathways, including p38 MAPK and PI3K/AKT/mTOR, in mediating OIS.
  • To explore the potential of targeting OIS for novel cancer therapeutic strategies.

Main Methods:

  • Literature review of recent studies on Oncogene-induced senescence.
  • Analysis of signaling pathways involved in OIS, focusing on p38 MAPK and PI3K/AKT/mTOR.
  • Discussion of the interplay between DNA damage response, chromatin remodeling, SASP, and OIS.

Main Results:

  • OIS is an essential anti-cancer mechanism that requires disruption for tumor development.
  • Key molecular players in OIS include the p53/p21(WAF1) and p16(INK4A) pathways.
  • The p38 MAPK and PI3K/AKT/mTOR pathways are integral components of the intricate signaling network governing OIS.

Conclusions:

  • OIS is a complex cellular response mediated by an intricate signaling network.
  • Further elucidation of OIS mechanisms, particularly the involved signaling pathways, is crucial.
  • Targeting OIS pathways holds promise for the development of innovative cancer therapies.
Keywords:
AKToncogene-induced senescencep38phosphoinositide 3-kinase

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