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Review
. 2018 Jan 30;23(2):285.
doi: 10.3390/molecules23020285.

PTEN Inhibition in Human Disease Therapy

Rafael Pulido  1   2
Affiliations
Review

PTEN Inhibition in Human Disease Therapy

Rafael Pulido. Molecules. .

Abstract

The tumor suppressor PTEN is a major homeostatic regulator, by virtue of its lipid phosphatase activity against phosphatidylinositol 3,4,5-trisphosphate [PI(3,4,5)P3], which downregulates the PI3K/AKT/mTOR prosurvival signaling, as well as by its protein phosphatase activity towards specific protein targets. PTEN catalytic activity is crucial to control cell growth under physiologic and pathologic situations, and it impacts not only in preventing tumor cell survival and proliferation, but also in restraining several cellular regeneration processes, such as those associated with nerve injury recovery, cardiac ischemia, or wound healing. In these conditions, inhibition of PTEN catalysis is being explored as a potentially beneficial therapeutic intervention. Here, an overview of human diseases and conditions in which PTEN inhibition could be beneficial is presented, together with an update on the current status of specific small molecule inhibitors of PTEN enzymatic activity, their use in experimental models, and their limitations as research or therapeutic drugs.

Keywords: cancer; diabetes; infertility; neuroregeneration; pain relief; response to infection; small molecule PTEN inhibitor; stem-cells; tissue injury; wound healing.

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Conflict of interest statement

The author declares no conflict of interest.

Figures

Figure 1
Figure 1
Schematic depiction of PTEN generic substrates. In the upper panel, dephosphorylation of PI(3,4,5)P3 at the plasma membrane is shown. In the bottom panel, protein dephosphorylation is shown, with the side chain of Ser, Thr, or Tyr amino acids in brackets. PI3K, phosphatidylinositol-4,5-bisphosphate 3-kinase; TK, tyrosine kinase.
Figure 2
Figure 2
Significance of PTEN inhibition in human disease therapy. Human diseases which could benefit from PTEN pharmacologic inhibition are indicated (see text for a more comprehensive description). Note that the potential beneficial effect of PTEN inhibition has been related with PTEN PI(3,4,5)P3 lipid phosphatase activity. Whether PTEN inhibition may be beneficial in some conditions in relation to PTEN protein phosphatase activity needs to be explored.
See this image and copyright information in PMC

References

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