Glycogen synthase kinase 3beta (GSK3beta) in tumorigenesis and cancer chemotherapy.

Glycogen synthase kinase 3beta (GSK3beta), 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 GSK3beta functions in diverse cellular processes including proliferation, differentiation, motility and survival. Aberrant regulation of GSK3beta 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 GSK3beta inhibitors has become an important area of investigation. However, GSK3beta also participates in neoplastic transformation and tumor development. The role of GSK3beta 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. GSK3beta also mediates drug sensitivity/resistance in cancer chemotherapy. Therefore, although GSK3beta 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 GSK3beta in tumorigenesis/cancer progression as well as its modulation of cancer chemotherapy.