Glycogen synthase kinase 3β in tumorigenesis and oncotherapy (Review)

Abstract

Glycogen synthase kinase 3β (GSK 3β), a multifunctional serine and threonine kinase, plays a critical role in a variety of cellular activities, including signaling transduction, protein and glycogen metabolism, cell proliferation, cell differentiation, and apoptosis. Therefore, aberrant regulation of GSK 3β results in a broad range of human diseases, such as tumors, diabetes, inflammation and neurodegenerative diseases. Accumulating evidence has suggested that GSK 3β is correlated with tumorigenesis and progression. However, GSK 3β is controversial due to its bifacial roles of tumor suppression and activation. In addition, overexpression of GSK 3β is involved in tumor growth, whereas it contributes to the cell sensitivity to chemotherapy. However, the underlying regulatory mechanisms of GSK 3β in tumorigenesis remain obscure and require further in-depth investigation. In this review, we comprehensively summarize the roles of GSK 3β in tumorigenesis and oncotherapy, and focus on its potentials as an available target in oncotherapy.

Nobiletin Induces Ferroptosis in Human Skin Melanoma Cells Through the GSK3β-Mediated Keap1/Nrf2/HO-1 Signalling Pathway

“…GSK3β, a serine/threonine protein kinase, is a key enzyme involved in various diseases, including cancer ( Domoto et al, 2020 ; He et al, 2020 ). Although the role of GSK3β in cancer has been extensively studied, it still remains controversial.…”

“…Glycogen synthase kinase 3β (GSK3β) is a ubiquitously expressed serine/threonine protein kinase involved in the regulation of various cellular biological processes, including glycogen metabolism, signal transduction, cell cycle regulation, and cell proliferation ( Theeuwes et al, 2017 ). Accumulating evidence suggests that GSK3β is a crucial regulator of the oxidative stress response associated with the occurrence and development of cancer ( Domoto et al, 2020 ; He et al, 2020 ). Recent studies have shown that overexpression of GSK3β promotes erastin-induced ferroptosis and increases the sensitivity of breast cancer cells to chemotherapeutic agents ( Wu et al, 2020 ).…”

Metabolites of Marine Sediment-Derived Fungi: Actual Trends of Biological Activity Studies

“…New bis-xanthone derivatives, secalonic acids H-M (114-119) were isolated from Penicillum oxalicum fungus (Langqi Island, Taiwan Strait). Secalonic acids H (114) and I (115) showed a weak cytotoxic effect toward HCT116, KB, and EC9706 cell lines [75], whereas compounds 116-119 exhibited moderate cytotoxicity against HeLa, HCT116, MCF-7, Hep-3B, and A549 cells. Moreover secalonic acid J (116), isolated from Penicillium oxalicum fungus, showed moderate induction of apoptosis in HeLa cells [76].…”

“…However, GSK 3 beta is controversial due to its bifacial roles of tumor suppression and activation. In addition, overexpression of GSK 3 beta is involved in tumor growth, and it contributes to cell sensitivity to chemotherapy [ 114 ]. Moreover, it was reported that Gsk-3 protein can be activated in SARS-CoV-2 viral infected cells which results in excessive oxidative stress via degradation of the nuclear factor erythroid 2-related factor (Nrf2) protein.…”

Excessive aggression, ADHD- and ASD-like phenotypes in TPH2- and brain ganglioside-deficient mice

“…This challenges the view that these transcripts play a pivotal role in the aggression elicited in stressed Tph2 +/− females [25,33] and further suggests that differences sex difference result in the differential regulation of aggression in the Tph2 +/− mice. For GSK-3β, given that the level of the phosphorylated form of this kinase is the principal determinant of its activity, activity has been shown to correlate with Gsk-3β gene expression changes [67]. However, the further assessment of the level of GSK-3β phosphorylation might be useful to -152 -confirm this association and its role in the behavioral abnormalities of Tph2 +/− females reported here.…”