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Regulation and modulation of PTEN activity

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Abstract

PTEN (Phosphatase and tensin homolog deleted on chromosome ten) is a tumor suppressor that is frequently mutated in most human cancers. PTEN is a lipid and protein phosphatase that antagonizes PI3K/AKT pathway through lipid phosphatase activity at the plasma membrane. More recent studies showed that, in addition to the putative role of PTEN as a PI(3,4,5)P3 3-phosphatase, it is a PI(3,4)P2 3-phosphatase during stimulation of class I PI3K signaling pathway by growth factor. Although PTEN tumor suppressor function via it’s lipid phosphatase activity occurs primarily in the plasma membrane, it can also be found in the nucleus, in cytoplasmic organelles and extracellular space. PTEN has also shown phosphatase independent functions in the nucleus. PTEN can exit from the cell through exosomal export or secretion and has a tumor suppressor function in adjacent cells. PTEN has a critical role in growth, the cell cycle, protein synthesis, survival, DNA repair and migration. Understanding the regulation of PTEN function, activity, stability, localization and its dysregulation outcomes and also the intracellular and extracellular role of PTEN and paracrine role of PTEN-L in tumor cells as an exogenous therapeutic agent can help to improve clinical conceptualization and treatment of cancer.

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Acknowledgements

This work funded by Tabriz University of Medical Sciences (Grant Code: 5/104/996). We thank the Stem Cell Research Center for technical support.

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Authors and Affiliations

  1. Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran

    Elahe Naderali & Hojjatollah Nozad Charoudeh

  2. Department of Anatomical sciences, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran

    Amir Afshin Khaki, Jafar Soleymani Rad & Alireza Ali-Hemmati

  3. Department of Clinical Biochemistry Sciences, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran

    Mohammad Rahmati

  4. Cell Therapy Research Laboratory, Drug Applied Research Center, Tabriz University of Medical Sciences, P.O. Box: 51656-65811, Tabriz, Iran

    Hojjatollah Nozad Charoudeh

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  1. Elahe Naderali
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Naderali, E., Khaki, A.A., Rad, J.S. et al. Regulation and modulation of PTEN activity. Mol Biol Rep 45, 2869–2881 (2018). https://doi.org/10.1007/s11033-018-4321-6

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