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Targeting PI3-Kinases in Modulating Autophagy and Anti-cancer Therapy

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Part of the Current Cancer Research book series (CUCR)

Abstract

Phosphoinositide 3-kinases (hereafter referred to as PI3-kinases) are lipid kinases that phosphorylate the 3′-hydroxyl group of inositol lipids. The generated phospholipids are critical signaling molecules that recruit proteins to specific intracellular membranes leading to localized activation of these proteins. PI3-kinases regulate many cellular activities, and are closely linked to human diseases, including cancer. One molecular event regulated by PI3-kinases is autophagy, an evolutionarily conserved membrane trafficking process that degrades and recycles cellular constituents to maintain cell and tissue homeostasis. Over the past two decades, our understanding of PI3-kinases has progressed from pan-PI3-kinase inhibitor studies to isoform-specific genetic knockout and systems biology interactome analyses. Our view of autophagy has emerged from unicellular yeast vesicle trafficking to mammalian physiology and human diseases. In this chapter we summarize the major discoveries on autophagy regulation by PI3-kinases and discuss the therapeutic potentials of targeting PI3-kinases in modulating autophagy and in cancer therapy.

Keywords

Autophagy PI3K Cancer therapy Chloroquine p110α p110β Vps34 

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Copyright information

© Springer International Publishing Switzerland 2016

Authors and Affiliations

  1. 1.Epigenetics Program, Department of Cell and Developmental BiologyPerelman School of Medicine, University of PennsylvaniaPhiladelphiaUSA
  2. 2.Department of Chemical BiologyErnest Mario School of Pharmacy, Rutgers UniversityPiscatawayUSA
  3. 3.Cancer Institute of New JerseyNew BrunswickUSA

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