Glycogen synthase kinase 3β (GSK3β) reportedly has opposing roles, repressing Wnt/β-catenin signaling on the one hand but maintaining cell survival and proliferation through the NF-κB pathway on the other. The present investigation was undertaken to clarify the roles of GSK3β in human cancer. In colon cancer cell lines and colorectal cancer patients, levels of GSK3β expression and amounts of its active form were higher in tumor cells than in their normal counterparts; these findings were independent of nuclear accumulation of β-catenin oncoprotein in the tumor cells. Inhibition of GSK3β activity by phosphorylation was defective in colorectal cancers but preserved in non-neoplastic cells and tissues. Strikingly, inhibition of GSK3β activity by chemical inhibitors and its expression by RNA interference targeting GSK3β induced apoptosis and attenuated proliferation of colon cancer cells in vitro. Our findings demonstrate an unrecognized role of GSK3β in tumor cell survival and proliferation other than its predicted role as a tumor suppressor, and warrant proposing this kinase as a potential therapeutic target in colorectal cancer.
|Original language||English (US)|
|Number of pages||9|
|Journal||Biochemical and Biophysical Research Communications|
|State||Published - Sep 9 2005|
Bibliographical noteFunding Information:
We thank Dr. Hiroyasu Esumi (National Cancer Center Research Institute, Japan) for reviewing the manuscript, and Mr. Michael Meyer for editorial assistance. This work was supported by Grants-in-Aid for Scientific Research from the Japanese Ministry of Education, Science, Sports, Technology and Culture (to T.M.), from the Ministry of Health, Labour and Welfare (to T.M.), and from the Japan Society for the Promotion of Science (to T.M., A.O., and B.Z.).
- Cell survival
- Colorectal cancer
- Glycogen synthase kinase 3β
- Therapeutic target
- Wnt signaling