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Trends Cancer. 2016 Jul;2(7):378-390. Epub 2016 Jun 20.

The Hidden Conundrum of Phosphoinositide Signaling in Cancer.

Author information

1
University of Wisconsin-Madison School of Medicine and Public Health, 1300 University Avenue, Madison, WI 53706, USA.
2
Program in Molecular and Cellular Pharmacology, 1300 University Avenue, Madison, WI 53706, USA.
3
Department of Oncology, 1300 University Avenue, Madison, WI 53706, USA; McArdle Laboratory for Cancer Research, 1300 University Avenue, Madison, WI 53706, USA; University of Wisconsin-Madison School of Medicine and Public Health, 1300 University Avenue, Madison, WI 53706, USA.
4
Program in Molecular and Cellular Pharmacology, 1300 University Avenue, Madison, WI 53706, USA; Department of Human Oncology, 1300 University Avenue, Madison, WI 53706, USA; University of Wisconsin-Madison School of Medicine and Public Health, 1300 University Avenue, Madison, WI 53706, USA.
5
Program in Molecular and Cellular Pharmacology, 1300 University Avenue, Madison, WI 53706, USA; University of Wisconsin-Madison School of Medicine and Public Health, 1300 University Avenue, Madison, WI 53706, USA.

Abstract

Phosphoinositide 3-kinase (PI3K) generation of PI(3,4,5)P3 from PI(4,5)P2 and the subsequent activation of Akt and its downstream signaling cascades (e.g. mTORC1) dominates the landscape of phosphoinositide signaling axis in cancer research. However, PI(4,5)P2 is breaking its boundary as merely a substrate for PI3K and phospholipase C (PLC), and is now an established lipid messenger pivotal for different cellular events in cancer. Here, we review the phosphoinositide signaling axis in cancer, giving due weight to PI(4,5)P2 and its generating enzymes, the phosphatidylinositol phosphate (PIP) kinases (PIPKs). We highlighted how PI(4,5)P2 and PIP kinases serve as a proximal node in phosphoinositide signaling axis and how its interaction with cytoskeletal proteins regulates migratory and invasive nexus of metastasizing tumor cells.

KEYWORDS:

Akt; PI(3,4,5)P3; PI(4,5)P2; PI3K; PIPKIγ

PMID:
27819060
PMCID:
PMC5094282
DOI:
10.1016/j.trecan.2016.05.009
[Indexed for MEDLINE]
Free PMC Article

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