The cross-talk of NOTCH and GSK-3 signaling in colon and other cancers

The GSK-3 kinases, GSK-3 alpha and GSK-3 beta, have a central role in regulating multiple cellular processes such as glycogen synthesis, insulin signaling, cell proliferation and apoptosis. GSK-3 beta is the most well studied, and was originally described for its role in regulating glycogen synthase. GSK-3 beta has been studied as a participant in the oncogenic process in a variety of cancers due to its intersection with the PTEN/PI3K/AKT and RAS/RAF/MEK/ERK pathways. Dysregulated signaling through the Notch family of receptors can also promote oncogenesis. Normal Notch receptor signaling regulates cell fate determination in stem cell pools. GSK-3 beta and Notch share similar targets such beta-catenin and the WNT pathway. WNT and beta-catenin are involved in several oncogenic processes including those of the colon. In addition, GSK-3 beta may directly regulate aspects of Notch signaling. This review describes how crosstalk between GSK-3 beta and Notch can promote oncogenesis, using colon cancer as the primary example.