title: Phosphoinositide-3-Kinase Enhancers, PIKEs: Their Biological Functions and Roles in Cancer.
abstract: 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.
authors.affiliation: Cardiff China Medical Research Collaborative, Cardiff University School of Medicine, Cardiff University, Cardiff, U.K. Breast Cancer Department, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, P.R. China.
authors.forename: Weijuan
authors.initials: W
authors.lastname: Jia
authors.affiliation: Cardiff China Medical Research Collaborative, Cardiff University School of Medicine, Cardiff University, Cardiff, U.K.
authors.forename: Y I
authors.initials: YI
authors.lastname: Feng
authors.affiliation: Cardiff China Medical Research Collaborative, Cardiff University School of Medicine, Cardiff University, Cardiff, U.K.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Sanders
authors.affiliation: Cardiff Breast Centre, University Hospital Llandough, Cardiff and Vale University Health Board, Cardiff, U.K.
authors.forename: Eleri L
authors.initials: EL
authors.lastname: Davies
authors.affiliation: Cardiff China Medical Research Collaborative, Cardiff University School of Medicine, Cardiff University, Cardiff, U.K. jiangW@cardiff.ac.uk.
authors.forename: Wen G
authors.initials: WG
authors.lastname: Jiang
mesh_terms: D000818:Animals; D002465:Cell Movement / Q000187:drug effects; D019204:GTP-Binding Proteins / Q000235:genetics* / Q000378:metabolism*; D020690:GTPase-Activating Proteins / Q000235:genetics* / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D058990:Molecular Targeted Therapy; D009154:Mutation; D009361:Neoplasm Invasiveness; D009369:Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000090063:Proto-Oncogene Mas; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D019204:GTP-Binding Proteins; D020690:GTPase-Activating Proteins; D019869:Phosphatidylinositol 3-Kinases; D000090063:Proto-Oncogene Mas; D051057:Proto-Oncogene Proteins c-akt; C000715470:MAS1 protein, human; C485997:AGAP2 protein, human
keywords: PI3K; PIKE; cancer; review