The lipid products of phosphoinositide 3-kinase isoforms in cancer and thrombosis

The lipid products of phosphoinositide 3-kinase isoforms in cancer and thrombosis Our knowledge on the role of the different lipid messengers produced by phosphoinositide 3-kinases (PI3Ks) in normal and cancer cells as well as in platelets during arterial thrombosis has greatly expanded these last 15 years. PI3Ks are a family of lipid kinases that catalyze the phosphorylation of the D3 position of the inositol ring of phosphoinositides to produce phosphatidylinositol 3-phosphate (PtdIns3P), phosphatidylinositol 3,4-bisphosphate (PtdIns(3,4)P2), and phosphatidylinositol-3,4,5 trisphosphate (PtdIns(3,4,5)P3). These D3-phosphoinositides act as intracellular messengers recruiting effector proteins involved in the control of diverse cellular functions including survival, proliferation, migration, membrane trafficking, and cytoskeleton dynamics. The current idea is that the different isoforms of PI3Ks produce specific pools of lipids that regulate in time and space, at the membrane/cytosol interface, the formation of appropriate functional protein complexes. Dysregulation of PI3K-dependent pathways is directly involved in the etiology of several pathologies including cancers where the PI3K/AKT/mTORC1 axis is frequently aberrantly activated. Moreover, PtdIns(3,4,5)P3 production has been shown to play an essential role in platelet functions, particularly in the formation of a stable platelet thrombus at high shear rate. Therefore, PI3Ks are attractive therapeutic targets in the treatment of cancer and arterial thrombosis. In this review, we will discuss the role of the different lipid products of PI3K isoforms in the context of cancer and thrombosis and the development of selective PI3Ks inhibitors in the treatment of these diseases. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Cancer and Metastasis Reviews Springer Journals

The lipid products of phosphoinositide 3-kinase isoforms in cancer and thrombosis

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Publisher
Springer Journals
Copyright
Copyright © 2018 by Springer Science+Business Media, LLC, part of Springer Nature
Subject
Biomedicine; Cancer Research; Oncology; Biomedicine, general
ISSN
0167-7659
eISSN
1573-7233
D.O.I.
10.1007/s10555-018-9735-z
Publisher site
See Article on Publisher Site

Abstract

Our knowledge on the role of the different lipid messengers produced by phosphoinositide 3-kinases (PI3Ks) in normal and cancer cells as well as in platelets during arterial thrombosis has greatly expanded these last 15 years. PI3Ks are a family of lipid kinases that catalyze the phosphorylation of the D3 position of the inositol ring of phosphoinositides to produce phosphatidylinositol 3-phosphate (PtdIns3P), phosphatidylinositol 3,4-bisphosphate (PtdIns(3,4)P2), and phosphatidylinositol-3,4,5 trisphosphate (PtdIns(3,4,5)P3). These D3-phosphoinositides act as intracellular messengers recruiting effector proteins involved in the control of diverse cellular functions including survival, proliferation, migration, membrane trafficking, and cytoskeleton dynamics. The current idea is that the different isoforms of PI3Ks produce specific pools of lipids that regulate in time and space, at the membrane/cytosol interface, the formation of appropriate functional protein complexes. Dysregulation of PI3K-dependent pathways is directly involved in the etiology of several pathologies including cancers where the PI3K/AKT/mTORC1 axis is frequently aberrantly activated. Moreover, PtdIns(3,4,5)P3 production has been shown to play an essential role in platelet functions, particularly in the formation of a stable platelet thrombus at high shear rate. Therefore, PI3Ks are attractive therapeutic targets in the treatment of cancer and arterial thrombosis. In this review, we will discuss the role of the different lipid products of PI3K isoforms in the context of cancer and thrombosis and the development of selective PI3Ks inhibitors in the treatment of these diseases.

Journal

Cancer and Metastasis ReviewsSpringer Journals

Published: Jun 4, 2018

References

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