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PI3K in stemness regulation: from development to cancer
1UCL Cancer Institute, Paul O'Gorman Building, University College London, 72 Huntley Street, London WC1E 6DD, U.K.
Biochemical Society Transactions
|February 4, 2020
Summary
The PI3K/AKT pathway regulates stemness in both pluripotent stem cells and cancer cells. Understanding this link is crucial for developing effective cancer therapies, as stemness can become treatment-resistant.
Area of Science:
- Oncology
- Developmental Biology
- Cell Signalling
Background:
- The PI3K/AKT pathway is a primary target in cancer, mainly studied for its role in cell proliferation and survival.
- Less attention has been given to the PI3K pathway's role in regulating stemness, despite its connection to therapeutic failure in cancer.
- Acquisition of stem cell-like features in cancer is increasingly linked to poor treatment outcomes.
Purpose of the Study:
- To review the known and unknown aspects of PI3K-dependent stemness regulation.
- To integrate knowledge from developmental, signalling, and cancer biology.
- To explore parallels between pluripotent stem cells (PSCs) and cancer stem cells.
Main Methods:
- Literature review integrating findings from developmental biology, signalling pathways, and cancer research.
- Analysis of the PI3K pathway's role in both mouse and human pluripotent stem cells (PSCs).
- Examination of cancer studies involving PI3K pathway activation and stemness phenotypes.
Main Results:
- PI3K/AKT signalling is integral to a core molecular stemness program in PSCs.
- Constitutive PI3K pathway activation, e.g., via PIK3CAH1047R, increases cancer stemness in a dose-dependent manner.
- Cancer stemness may become "locked" and independent of PI3K activation, limiting monotherapy efficacy.
Conclusions:
- The PI3K pathway plays a critical role in regulating stemness in both normal and cancerous cells.
- Understanding the dual role of PI3K in cell growth and stemness is essential for advancing cancer therapeutics.
- Context-dependent regulation of PI3K is key to overcoming therapeutic resistance driven by cancer stemness.
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