GSK-3 as potential target for therapeutic intervention in cancer
McCubrey, James A.; Steelman, Linda S.; Bertrand, Fred E.; Davis, Nicole M.; Sokolosky, Melissa; Abrams, Stephen L.; Montalto, Giuseppe; D'Assoro, Antonino B.; Libra, Massimo; Nicoletti, Ferdinando; Maestro, Roberta; Basecke, Jorg; Rakus, Dariusz; Gizak, Agnieszka; Demidenko, Zoya; Cocco, Lucio; Martelli, Alberto M.; Cervello, Melchiorre
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.
McCubrey, James A., & Steelman, Linda S., & Bertrand, Fred E., & Davis, Nicole M., & Sokolosky, Melissa, & Abrams, Stephen L., & Montalto, Giuseppe, & D'Assoro, Antonino B., & Libra, Massimo, & Nicoletti, Ferdinando, & Maestro, Roberta, & Basecke, Jorg, & Rakus, Dariusz, & Gizak, Agnieszka, & Demidenko, Zoya, & Cocco, Lucio, & Martelli, Alberto M., & Cervello, Melchiorre. (May 2014). GSK-3 as potential target for therapeutic intervention in cancer. Oncotarget, 5(10), 2881- 2911. Retrieved from http://hdl.handle.net/10342/5659
McCubrey, James A., and Steelman, Linda S., and Bertrand, Fred E., and Davis, Nicole M., and Sokolosky, Melissa, and Abrams, Stephen L., and Montalto, Giuseppe, and D'Assoro, Antonino B., and Libra, Massimo, and Nicoletti, Ferdinando, and Maestro, Roberta, and Basecke, Jorg, and Rakus, Dariusz, and Gizak, Agnieszka, and Demidenko, Zoya, and Cocco, Lucio, and Martelli, Alberto M., and Cervello, Melchiorre. "GSK-3 as potential target for therapeutic intervention in cancer". Oncotarget. 5:10. (2881-2911), May 2014. February 15, 2019. http://hdl.handle.net/10342/5659.
McCubrey, James A. and Steelman, Linda S. and Bertrand, Fred E. and Davis, Nicole M. and Sokolosky, Melissa and Abrams, Stephen L. and Montalto, Giuseppe and D'Assoro, Antonino B. and Libra, Massimo and Nicoletti, Ferdinando and Maestro, Roberta and Basecke, Jorg and Rakus, Dariusz and Gizak, Agnieszka and Demidenko, Zoya and Cocco, Lucio and Martelli, Alberto M. and Cervello, Melchiorre, "GSK-3 as potential target for therapeutic intervention in cancer," Oncotarget 5, no. 10 (May 2014), http://hdl.handle.net/10342/5659 (accessed February 15, 2019).
McCubrey, James A., Steelman, Linda S., Bertrand, Fred E., Davis, Nicole M., Sokolosky, Melissa, Abrams, Stephen L., Montalto, Giuseppe, D'Assoro, Antonino B., Libra, Massimo, Nicoletti, Ferdinando, Maestro, Roberta, Basecke, Jorg, Rakus, Dariusz, Gizak, Agnieszka, Demidenko, Zoya, Cocco, Lucio, Martelli, Alberto M., Cervello, Melchiorre. GSK-3 as potential target for therapeutic intervention in cancer. Oncotarget. May 2014; 5(10): 2881-2911. http://hdl.handle.net/10342/5659. Accessed February 15, 2019.