GSK-3 as potential target for therapeutic irvention in cancer

Academic Article

Abstract

  • The serine/threonine kinase glycogen synthase kinase-3 (GSK-3) was initially identified and studied in the regulation of glycogen synthesis. GSK-3 functions in a wide range of cellular processes. Aberrant activity of GSK-3 has been implicated in many human pathologies including: bipolar depression, Alzheimer's disease, Parkinson's disease, cancer, non-insulin-dependent diabetes mellitus (NIDDM) and others. In some cases, suppression of GSK-3 activity by phosphorylation by Akt and other kinases has been associated with cancer progression. In these cases, GSK-3 has tumor suppressor functions. In other cases, GSK-3 has been associated with tumor progression by stabilizing components of the beta-catenin complex. In these situations, GSK-3 has oncogenic properties. While many inhibitors to GSK-3 have been developed, their use remains controversial because of the ambiguous role of GSK-3 in cancer development. In this review, we will focus on the diverse roles that GSK-3 plays in various human cancers, in particular in solid tumors. Recently, GSK-3 has also been implicated in the generation of cancer stem cells in various cell types. We will also discuss how this pivotal kinase interacts with multiple signaling pathways such as: PI3K/PTEN/Akt/mTORC1, Ras/Raf/MEK/ERK, Wnt/beta-catenin, Hedgehog, Notch and others. © 2008-2014 Impact Journals, LLC.
  • Published In

  • Oncotarget  Journal
  • Digital Object Identifier (doi)

    Author List

  • Mccubrey JA; Steelman LS; Bertrand FE; Davis NM; Sokolosky M; Abrams SL; Montalto G; D'Assoro AB; Libra M; Nicoletti F
  • Start Page

  • 2881
  • End Page

  • 2911
  • Volume

  • 5
  • Issue

  • 10