Role of GSK3 (glycogen synthase kinase 3) as tumor promoter and tumor suppressor - A review

Abstract

Glycogen synthase kinase 3? (GSK3?), a multifunctional serine/threonine kinase found in all eukaryotes, had been initially identified as a key regulator of insulin-dependent glycogen synthesis. It is now known that GSK3? functions in diverse cellular processes including proliferation, differentiation, motility and survival. Aberrant regulation of GSK3? has been implicated in a range of human pathologies including non-insulin-dependent diabetes mellitus, cardiovascular disease, some neurodegenerative diseases, and bipolar disorder. As a consequence, the therapeutic potential of GSK3? inhibitors has become an important area of investigation. However, GSK3? also participates in neoplastic transformation and tumor development. The role of GSK3? in tumorigenesis and cancer progression remains controversial; it may function as a �tumor suppressor� for certain types of tumors, but promotes growth and development for some others. GSK3? also mediates drug sensitivity/resistance in cancer chemotherapy. Therefore, although GSK3? is an attractive therapeutic target for a number of human diseases, its potential impact on tumorigenesis and cancer chemotherapy needs to be carefully evaluated. This mini-review discusses the role of GSK3? in tumorigenesis/cancer progression as well as its modulation of cancer chemotherapy.