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SOX2 and p53 Expression Control Converges in PI3K/AKT Signaling with Versatile Implications for Stemness and Cancer

Thorsten Schaefer1, Rebekah Steiner2, Claudia Lengerke1,3

  • 1Stem Cells & Hematopoiesis Laboratory, Department of Biomedicine, University of Basel and University Hospital Basel, CH-4031 Basel, Switzerland.

International Journal of Molecular Sciences
|July 16, 2020
PubMed

Insights

Stemness relies on SOX2 regulation by the PI3K/AKT pathway, which also impacts DNA damage response via p53. This balance is crucial for stem cell function and cancer development.

Area of Science:

  • Stem cell biology
  • Molecular oncology
  • Signaling pathways

Background:

  • Stemness, characterized by self-renewal and suppressed differentiation, is regulated by master transcription factors like SOX2.
  • The PI3K/AKT signaling pathway plays a critical role in stem cell maintenance, influencing SOX2 localization and turnover.
  • Apoptosis, a key component of DNA damage response (DDR), is regulated by tumor suppressor p53 and counteracted by PI3K/AKT signaling.

Purpose of the Study:

  • To review the interplay between PI3K/AKT/SOX2-driven stemness and p53-mediated DDR.
  • To highlight the significance of these pathways in pluripotency, cellular reprogramming, and cancer development.
  • To summarize recent advances in understanding these molecular mechanisms.

Main Methods:

  • Literature review of studies on stemness, SOX2, PI3K/AKT signaling, p53, and DNA damage response.
  • Analysis of molecular mechanisms connecting these pathways in various cell types (ESCs, iPSCs, CSCs).
  • Focus on the functional overlap and implications in genomic integrity and transformation.

Main Results:

  • The PI3K/AKT/SOX2 axis is a stem cell-specific pathway regulating SOX2, cell cycle, growth, and apoptosis.
  • SOX2 expression and p53-dependent DDR mechanisms share molecular-functional links within PI3K/AKT signaling.
  • Genomic instability in stem cells, potentially exacerbated by reprogramming (iPSCs), can lead to cancer.

Conclusions:

  • The intricate relationship between stemness regulators (SOX2) and DNA damage response (p53) via PI3K/AKT signaling is vital for stem cell homeostasis.
  • Dysregulation of this balance poses risks for genomic integrity, contributing to cancer initiation and progression.
  • Understanding these pathways offers insights into stem cell biology, reprogramming, and therapeutic strategies for cancer.
Keywords:
DNA damage response (DDR)DNA maintenancePI3K/AKT signalingSOX2cancergenome integrityp53pluripotencystem cellstransformation

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