ReviewInternational journal of molecular sciences2020
SOX2 and p53 Expression Control Converges in PI3K/AKT Signaling with Versatile Implications for Stemness and Cancer.
Review in International journal of molecular sciences, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed.
- Understanding the molecular basis of mesenchymal stem cell stemness: implications for clinical applications.Cell death & disease · 2025Review
- Reversing the Warburg Effect: YW3-56 Induces Leukemia Differentiation via AKT-Mediated Glucose Metabolic Reprogramming.Pharmaceuticals (Basel, Switzerland) · 2025Article
- Signaling pathways as the pivotal regulators of cisplatin resistance in tumor cells through SOX2 upregulation.Medical oncology (Northwood, London, England) · 2025Review
- The Role of PI3K/AKT/mTOR Signaling in Tumor Radioresistance and Advances in Inhibitor Research.International journal of molecular sciences · 2025Review
- DNA-methylation eraser TET2 activates WTIP expression to suppress an AKT-dependent chemoresistance of gastric cancer.Neoplasia (New York, N.Y.) · 2025Article
- SOX2, PIWI proteins, and MALAT1 - plasma-based emerging biomarkers for cancer detection and monitoring.PloS one · 2025Article
- WD repeat domain 82 (Wdr82) facilitates mouse iPSCs generation by interfering mitochondrial oxidative phosphorylation and glycolysis.Cellular and molecular life sciences : CMLS · 2023Article
- Delta/Notch-like Epidermal Growth Factor-Related Receptor (DNER), a Potential Prognostic Marker of Gastric Cancer Regulates Cell Survival and Cell Cycle Progression.International journal of molecular sciences · 2023Article
- A Simplified and Effective Approach for the Isolation of Small Pluripotent Stem Cells Derived from Human Peripheral Blood.Biomedicines · 2023Article
- Androgen receptor variant 7 exacerbates hepatocarcinogenesis in a c-MYC-driven mouse HCC model.Oncogenesis · 2023Article
- Cisplatin Induces Senescent Lung Cancer Cell-Mediated Stemness Induction via GRP78/Akt-Dependent Mechanism.Biomedicines · 2022Article
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- Electromagnetic field exposure as a plausible approach to enhance the proliferation and differentiation of mesenchymal stem cells in clinically relevant scenarios.Journal of Zhejiang University. Science. B · 2022Review
- Biological Functions and Molecular Mechanisms of MiR-608 in Cancer.Frontiers in oncology · 2022Review
- Immune cells transcriptome-based drug repositioning for multiple sclerosis.Frontiers in immunology · 2022Article
- Hydroquinone 5-Pharmaceuticals (Basel, Switzerland) · 2021Article
- New Therapeutic Opportunities for the Treatment of Squamous Cell Carcinomas: A Focus on Novel Driver Kinases.International journal of molecular sciences · 2021Review
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Corrections and comments
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Authors and funding
3 authors.
Funding
Abstract
Stemness and reprogramming involve transcriptional master regulators that suppress cell differentiation while promoting self-renewal. A distinguished example thereof is SOX2, a high mobility group (HMG)-box transcription factor (TF), whose subcellular localization and turnover regulation in embryonic, induced-pluripotent, and cancer stem cells (ESCs, iPSCs, and CSCs, respectively) is mediated by the PI3K/AKT/SOX2 axis, a stem cell-specific branch of the PI3K/AKT signaling pathway. Further effector functions associated with PI3K/AKT induction include cell cycle progression, cellular (mass) growth, and the suppression of apoptosis. Apoptosis, however, is a central element of DNA damage response (DDR), where it provides a default mechanism for cell clearance when DNA integrity cannot be maintained. A key player in DDR is tumor suppressor p53, which accumulates upon DNA-damage and is counter-balanced by PI3K/AKT enforced turnover. Accordingly, stemness sustaining SOX2 expression and p53-dependent DDR mechanisms show molecular-functional overlap in PI3K/AKT signaling. This constellation proves challenging for stem cells whose genomic integrity is a functional imperative for normative ontogenesis. Unresolved mutations in stem and early progenitor cells may in fact provoke transformation and cancer development. Such mechanisms are also particularly relevant for iPSCs, where genetic changes imposed through somatic cell reprogramming may promote DNA damage. The current review aims to summarize the latest advances in the understanding of PI3K/AKT/SOX2-driven stemness and its intertwined relations to p53-signaling in DDR under conditions of pluripotency, reprogramming, and transformation.
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Registered trials
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