Involvement of PI3K/Akt pathway in cell cycle progression, apoptosis, and neoplastic transformation: a target for cancer chemotherapy
Abstract
The PI3K/Akt signal transduction cascade has been investigated extensively for its roles in oncogenic transformation. Initial studies implicated both PI3K and Akt in prevention of apoptosis. However, more recent evidence has also associated this pathway with regulation of cell cycle progression. Uncovering the signaling network spanning from extracellular environment to the nucleus should illuminate biochemical events contributing to malignant transformation. Here, we discuss PI3K/Akt-mediated signal transduction including its mechanisms of activation, signal transducing molecules, and effects on gene expression that contribute to tumorigenesis. Effects of PI3K/Akt signaling on important proteins controlling cellular proliferation are emphasized. These targets include cyclins, cyclin-dependent kinases, and cyclin-dependent kinase inhibitors. Furthermore, strategies used to inhibit the PI3K/Akt pathway are presented. The potential for cancer treatment with agents inhibiting this pathway is also addressed.
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Many authors have reported the effect of the secretome of MSCs on tumor cell proliferation and invasion in vitro and in vivo.
“many authors have been reported the effect of the secretome of MSCs in tumor cell proliferation and invasion in vitro and in vivo [104], [105], [106], [107].”
From Mesenchymal stem cell secretome for regenerative medicine: Where do we stand? (2025) · cites this paper as [104]
TBX3 has previously been shown to directly interact with these signaling cascades in other cell types to regulate cell survival and proliferation.
“TBX3 has previously been shown to directly interact with these signaling cascades in other cell types to regulate cell survival and proliferation [54–57]”
From The oncoprotein TBX3 is controlling severity in experimental arthritis (2019) · cites this paper as [54]
Activation of mitogenic pathways such as PI3K-AKT by inflammatory signals induces post-translational modifications of cell cycle regulatory proteins to potentiate cell cycle progression.
“it is well known that the activation of mitogenic pathways such as PI3K-AKT by inflammatory signals induces the necessary post-translational modifications (e.g., phosphorylation) of cell cycle regulatory proteins to potentiate cell cycle progression (Chang et al., 2003; Pietras et al., 2011; Warr et al., 2011; Pietras et al., 2014).”
From PU.1 is required to restrain myelopoiesis during chronic inflammatory stress (2023) · cites this paper as Chang et al., 2003
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“, phosphorylation) of cell cycle regulatory proteins to potentiate cell cycle progression (Chang et al., 2003; Pietras et al., 2011; Warr et al., 2011; Pietras et al., 2014).”
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- Authors
- Chang, F., Lee, J. T., Navolanic, P. M., Steelman, L. S., Shelton, J. G., Blalock, W. L., Franklin, R. A., & McCubrey, J. A.
- Affiliations
- East Carolina University (US)
- University of Florida Health (US)
- Venue
- Leukemia
- Published
- 2003-03-01
- Volume
- 17
- Issue
- 3
- Pages
- 590-603
- ISSN
- 0887-6924 (ISSN-L)
- 1476-5551
- OpenAlex
- W2170839629
- Cited by
- 1,176
- References
- 4
- Citations by year
- 2026: 17 · 2025: 41 · 2024: 48 · 2023: 52 · 2022: 74 · 2021: 74 · 2020: 68 · 2019: 69 · 2018: 69 · 2017: 58 · 2016: 65 · 2015: 59 · 2014: 65 · 2013: 50 · 2012: 42
- FWCI
- 3.42
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Leukemia (publishedVersion)
- PubMed (publishedVersion)
- Funders
- American Cancer Society
- National Institutes of Health
- National Cancer Institute (R01CA051025)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Signaling Pathways in Disease
- Keywords
- PI3K/Akt signaling, oncogenic transformation, apoptosis, cell cycle progression, cyclins, cyclin-dependent kinases, cyclin-dependent kinase inhibitors, signal transduction, carcinogenesis, PI3K inhibitors, AKT inhibitors, cancer chemotherapy
- MeSH terms
- Antineoplastic Agents, Cell Cycle, Cell Transformation, Neoplastic, Humans, Proto-Oncogene Proteins, Apoptosis, Protein Serine-Threonine Kinases, Phosphatidylinositol 3-Kinases, Proto-Oncogene Proteins c-akt
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