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Molecular Targets for Therapy (MTT)

Involvement of PI3K/Akt pathway in cell cycle progression, apoptosis, and neoplastic transformation: a target for cancer chemotherapy

Leukemia volume 17, pages 590–603 (2003)Cite this article

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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Acknowledgements

We thank Ms Catherine Spruill for the excellent artwork. This work was supported by grants from the United States National Institutes of Health (R01CA51025) and grants from the North Carolina Biotechnology Center (9805-ARG-0006, 2000-ARG-0003) to JAM. RAF was supported in part by grants from the American Cancer Society (IRG-97-149), American Heart Association (9930099N), and the North Carolina Biotechnology Center (9705-ARG-0009).

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  1. F Chang and J T Lee: The first two authors contributed equally to this work.

Authors and Affiliations

  1. Department of Microbiology & Immunology, Brody School of Medicine at East Carolina University, Greenville, NC, USA

    F Chang, J T Lee, P M Navolanic, L S Steelman, J G Shelton, R A Franklin & J A McCubrey

  2. Shands Cancer Center, University of Florida, Gainesville, FL, USA

    W L Blalock

  3. Leo Jenkins Cancer Center, Brody School of Medicine at East Carolina University, Greenville, NC, USA

    R A Franklin & J A McCubrey

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Chang, F., Lee, J., Navolanic, P. et al. Involvement of PI3K/Akt pathway in cell cycle progression, apoptosis, and neoplastic transformation: a target for cancer chemotherapy. Leukemia 17, 590–603 (2003). https://doi.org/10.1038/sj.leu.2402824

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