Phosphoinositide-3-Kinase Enhancers, PIKEs: Their Biological Functions and Roles in Cancer

Phosphoinositide 3-kinase enhancer (PIKE) belongs to a family of GTP-binding proteins, including three isoforms, PIKE-S, PIKE-L and PIKE-A. PIKE-S and PIKE-L interact with PI3K to enhance the activity of PI3K, but PIKE-A directly binds to AKT and up-regulates its activity. PIKEs also interacts with a variety of signaling molecules in addition to PI3K and AKT, to trigger multiple physiological functions. Overexpression or mutation of PIKE has been observed in a variety of tumors, especially PIKE-A, which acts as a proto-oncogene, promoting cancer cell growth, transformation and invasion through AKT signaling. Knockdown of PIKE-A or blocking of PIKE-A/AKT interactions enhances apoptosis, inhibits cancer cell proliferation, migration and invasion. Moreover, PIKE plays an important role in tumorigenesis through other signaling pathways, such as focal adhesion kinase, signal transducer and activator of transcription 5A, and nuclear factor kappa-light-chain-enhancer of activated B cells. The current review explores the functional role of PIKE and its potential in cancer therapy.