title: Power of PTEN/AKT: Molecular switch between tumor suppressors and oncogenes.
abstract: An increasing amount of evidence has shown that tumor suppressors can become oncogenes, or vice versa, but the mechanism behind this is unclear. Recent findings have suggested that phosphatase and tensin homolog (PTEN) is one of the powerful switches for the conversion between tumor suppressors and oncogenes. PTEN regulates a number of cellular processes, including cell death and proliferation, through the phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) pathway. Furthermore, a number of studies have suggested that PTEN deletions may alter various functions of certain tumor suppressor and oncogenic proteins. The aim of the present review was to analyze specific cases driven by PTEN loss/AKT activation, including aberrant signaling pathways and novel drug targets for clinical application in personalized medicine. The findings illustrate how PTEN loss and/or AKT activation switches MDM2-dependent p53 downregulation, and induces conversion between oncogene and tumor suppressor in enhancer of zeste homolog 2, BTB domain-containing 7A, alternative reading frame 2, p27 and breast cancer 1, early onset, through multiple mechanisms. This review highlights the genetic basis of complex drug targets and provides insights into the rationale of precision cancer therapy.
authors.affiliation: Department of Biology, Nazarbayev University, School of Science and Technology, Astana 010000, Republic of Kazakhstan.
authors.forename: Yingqiu
authors.initials: Y
authors.lastname: Xie
authors.affiliation: Department of Biology, Nazarbayev University, School of Science and Technology, Astana 010000, Republic of Kazakhstan.
authors.forename: Sanzhar
authors.initials: S
authors.lastname: Naizabekov
authors.affiliation: Lipscomb University, Lipscomb Academy, Nashville, TN 37204, USA.
authors.forename: Zhanlin
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Center for Life Sciences, National Laboratory Astana, Nazarbayev University, Astana 010000, Republic of Kazakhstan.
authors.forename: Tursonjan
authors.initials: T
authors.lastname: Tokay
keywords: PTEN; molecular switch; oncogene; tumor suppressor