Abstract
Glycogen synthase kinase 3 (GSK3) is a monomeric serine-threonine kinase discovered in 1980 in a rat skeletal muscle. It has been involved in various cellular processes including embryogenesis, immune response, inflammation, apoptosis, autophagy, wound healing, neurodegeneration, and carcinogenesis. GSK3 exists in two different isoforms, GSK3α and GSK3β, both containing seven antiparallel beta-plates, a short linking part and an alpha helix, but coded by different genes and variously expressed in human tissues. In the current review, we comprehensively appraise the current literature on the role of GSK3 in various cancers with emphasis on ovarian carcinoma. Our findings indicate that the role of GSK3 in ovarian cancer development cannot be decisively determined as the currently available data support both prooncogenic and tumor-suppressive effects. Likewise, the clinical impact of GSK3 expression on ovarian cancer patients and its potential therapeutic implications are also limited. Further studies are needed to fully elucidate the pathophysiological and clinical implications of GSK3 activity in ovarian cancer.
Highlights
According to the European Union (EU) statistics, almost 30,000 women died due to ovarian cancer throughout the Union in 2018
The role of GSK3β in epithelial-mesenchymal transition (EMT) suppression is strongly supported by the fact that compounds that reduce serine 9 phosphorylation of the enzyme inhibit EMT in ovarian cancer cell lines (Table 1) [104,105,106]
In contrast to Cao et al, who found reduced cell number and reduced cyclin D expression after exposure to lithium chloride (LiCl), as well as reduced tumor mass in vivo, more recent study by Novetsky et al found a minimal activity of LiCl toward tumor mass reduction and insignificant effects of LiCl when combined with paclitaxel or cisplatin
Summary
According to the European Union (EU) statistics, almost 30,000 women died due to ovarian cancer throughout the Union in 2018. GSK3β inhibition in pancreatic cancer cells suppresses Rb phosphorylation by cyclin D/cyclin-dependent kinase 4 or 6 complex and its subsequent degradation [62]. Cao et al found a higher immunohistochemical expression of GSK3β in ovarian cancer cells, whereas expression of the enzyme phosphorylated on serine 9 (pGSK3β-S9) varied among two cell lines included in the study.
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