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) dominate the landscape of the 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 various 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 (PI) phosphate (PIP) kinases (PIPKs). We highlight how PI(4,5)P2 and PIPKs serve as a proximal node in the phosphoinositide signaling axis and how interaction with cytoskeletal proteins regulates the migratory and invasive nexus of metastasizing tumor cells.
ASJC Scopus subject areas
- Cancer Research