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Absolute Quantitation of Inositol Pyrophosphates by Capillary Electrophoresis Electrospray Ionization Mass Spectrometry
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New Functions of the Inositol Polyphosphate 5-Phosphatases in Cancer

Christophe Erneux1, Somadri Ghosh, Ana Raquel Ramos

  • 1Interdisciplinary Research Institute (IRIBHM), Université Libre de Bruxelles, Campus Erasme, Bldg C, 808 Route de Lennik, 1070 Brussels, Belgium. cerneux@ulb.ac.be.

Current Pharmaceutical Design
|February 27, 2016
PubMed

Insights

Inositol 5-phosphatases regulate crucial cell signaling pathways. New activators and inhibitors offer potential treatments for cancer and inflammation.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Background:

  • Inositol polyphosphate 5-phosphatases are enzymes acting on inositol phosphates and phosphoinositides.
  • They comprise 10 human isoenzymes and splice variants implicated in pathologies like cancer and genetic syndromes.
  • Unlike tumor suppressors PTEN and INPP4B, 5-phosphatases are often amplified in cancer cells.

Purpose of the Study:

  • To investigate the role of inositol 5-phosphatases in cellular signaling and human diseases.
  • To understand their involvement in phosphoinositide metabolism and its impact on cellular functions.
  • To explore the potential of novel modulators for therapeutic applications.

Main Methods:

  • Analysis of inositol 5-phosphatase activity and expression.
  • Investigation of phosphoinositide lipid signaling networks.
  • Identification and characterization of novel enzyme inhibitors and activators.

Main Results:

  • Inositol 5-phosphatases critically influence phosphoinositide levels, including PI(3,4,5)P3, PI(4,5)P2, and PI(3,4)P2.
  • The dephosphorylation of PI(3,4,5)P3 to PI(3,4)P2 generates a key signaling molecule for cell migration, invasion, and endocytosis.
  • These enzymes impact intracellular targets like protein kinase B (PKB/Akt) and actin-binding proteins.

Conclusions:

  • Inositol 5-phosphatases are vital regulators of cellular processes and are dysregulated in various human cancers.
  • Targeting these enzymes with new inhibitors or activators holds promise for treating inflammatory diseases and cancer.
  • Further research into this enzyme family could unveil new therapeutic strategies.

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