The Hidden Conundrum of Phosphoinositide Signaling in Cancer.
Phosphoinositide 3-kinase (PI3K) generation of PI(3,4,5)P3from PI(4,5)P2and 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)P2is 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)P2and its generating enzymes, the phosphatidylinositol phosphate (PIP) kinases (PIPKs). We highlighted how PI(4,5)P2and 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.
University of Wisconsin-Madison School of Medicine and Public Health, 1300 University Avenue, Madison, WI 53706, USA.
Narendra
N
Thapa
Program in Molecular and Cellular Pharmacology, 1300 University Avenue, Madison, WI 53706, USA.
Xiaojun
X
Tan
University of Wisconsin-Madison School of Medicine and Public Health, 1300 University Avenue, Madison, WI 53706, USA.
Suyong
S
Choi
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.
Paul F
PF
Lambert
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.
Alan C
AC
Rapraeger
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.
Richard A
RA
Anderson
D000818:Animals; D002465:Cell Movement; D016764:Cell Polarity; D003599:Cytoskeleton / Q000378:metabolism; D006801:Humans; D009369:Neoplasms / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010716:Phosphatidylinositols / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction
D010716:Phosphatidylinositols; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt
Akt; PI(3,4,5)P3; PI(4,5)P2; PI3K; PIPKIγ