What is the role of GSK3 in cancer development and progression?
Best insight from top research papers
Glycogen synthase kinase 3 (GSK3) plays a significant role in cancer development and progression. GSK3 has been implicated in various aspects of tumorigenesis, including tumor progression, treatment resistance, and tumor angiogenesis . While initially considered a tumor suppressor due to its role in facilitating the destruction of oncogenic proteins, recent studies have shown that GSK3 isoforms can also act as tumor promoters in certain cancer settings . In lung cancer, GSK3α overexpression has been linked to promoting proliferation, migration, invasion, and clone formation ability of cancer cells, highlighting its oncogenic potential . Additionally, inhibition of GSK3 has shown promising preclinical antitumor activity, promoting immune cell-mediated tumor cell killing and enhancing immune responses, suggesting a potential therapeutic strategy in cancer treatment .
Answers from top 5 papers
More filters
| Papers (5) | Insight |
|---|---|
| GSK3's role in cancer is complex, showing both pro-oncogenic and tumor-suppressive effects. Its impact on ovarian cancer remains inconclusive, requiring further research for clarity on its pathophysiological implications. | |
| GSK-3 plays dual roles in cancer, acting as both a tumor suppressor and promoter by regulating key oncogenic proteins, such as β-catenin and c-Myc, influencing cancer cell pathobiology. | |
| GSK3α promotes tumorigenesis in NSCLC by activating the HIF1/VEGFA signaling pathway independently through the PHDs-pVHL pathway, enhancing proliferation, migration, invasion, and angiogenesis. | |
| GSK3α acts as an oncogene in NSCLC by activating the HIF1/VEGFA signaling pathway independently through the PHDs-pVHL pathway, promoting tumorigenesis and angiogenesis. | |
| GSK-3 plays a crucial role in tumor progression. Inhibition by elraglusib enhances immune cell activation, tumor cell killing, and synergizes with anti-PD-L1, suggesting potential in cancer therapy. |
Related Questions
Does the expression of GSK-3 in tumors depend on the presence of specific factors?5 answersThe expression of Glycogen Synthase Kinase-3 (GSK-3) in tumors is influenced by various factors. Studies have shown that GSK-3 expression is increased in cancer cells compared to normal cells, with active GSK-3 promoting the survival of gastrointestinal cancer cells through modulation of telomerase activity. In lung adenocarcinoma, GSK-3β expression correlates with specific molecular features like PTEN expression, PDL1 score, and driver mutations, impacting overall survival. Additionally, GSK-3 inhibition has been linked to decreased tumor cell survival and proliferation, as well as increased apoptosis in various cancer cell lines. These findings suggest that the expression and activity of GSK-3 in tumors depend on a complex interplay of factors including molecular characteristics, immune response markers, and cell survival pathways.
How does GSK-3 activation contribute to inflammation?4 answersGSK-3 activation contributes to inflammation by preventing the termination of TNF-induced signaling. It plays a crucial role in regulating pro-inflammatory cytokine/chemokine profiles, bacterial/viral infections, and associated pro-inflammatory transcriptional and signaling pathways. Activation of GSK-3 leads to pro-inflammatory actions, increased NF-κB binding activity, and enhanced transactivation activity of NF-κB, promoting inflammation-related diseases like diabetes, cancer, and neurodegenerative disorders. In chronic rhinosinusitis without nasal polyps (CRSsNP), insufficient inhibitory phosphorylation of GSK-3β correlates with recurrent inflammation, emphasizing its pivotal role in the pathogenesis of the condition. GSK-3 also regulates inflammatory processes by inducing the expression of various cytokines through NF-κB, making it a potential therapeutic target for inflammatory diseases.
What is the role of GSK-3 in the development of thymocytes?5 answersGSK-3 plays a crucial role in the development of thymocytes. T cell-specific ablation of GSK-3 leads to impaired thymic egress, preventing the emigration of thymocytes from the thymus to the periphery. Simultaneous inactivation of both GSK-3 and GSK-3β during early thymocyte ontogeny affects β-selection and positive selection, resulting in compromised TCRβ chain expression and reduced Notch activity. GSK-3 inhibition prevents UV-induced hyperphosphorylation of the carboxy terminal domain (CTD) of RNA polymerase II, inhibits transcriptional elongation, and changes alternative splicing due to kinetic coupling between transcription and splicing. Inhibition of GSK-3 promotes the developmental progression of DN3 thymocytes, allowing differentiation in the absence of pre-TCR, Notch1, or CXCL12-mediated signaling. Overall, GSK-3 is involved in multiple checkpoints of early T cell development, including thymic egress, β-selection, positive selection, and transcriptional elongation.
What does GSK3b do to wnt signaling pathway?5 answersGSK3β plays a role in the Wnt signaling pathway by negatively regulating it. It phosphorylates β-catenin, leading to its degradation and preventing its accumulation. GSK3β also inhibits the canonical Wnt/β-catenin signaling pathway by phosphorylating other components of the pathway, such as the TSC complex. However, GSK3β is insulated from cross-activation by other signaling pathways, such as the PI3K pathway, through the action of scaffold proteins like Axin. These scaffold proteins protect GSK3β from phosphorylation at Ser9, which prevents the accumulation of pS9-GSK3β in the Axin-GSK3β complex. Additionally, GSK3β has a positive role in promoting Wnt signaling at the plasma membrane, where it activates signaling in Drosophila embryos. Overall, GSK3β has complex interactions with the Wnt signaling pathway, both negatively regulating it and promoting its activation in different contexts.
What is the role of the protein PIK3CA in the development of colorectal cancer?5 answersPIK3CA, a gene encoding the p110α catalytic subunit of phosphatidylinositide-3-kinase (PI3K), plays an important role in colorectal cancer (CRC) development. Mutations in PIK3CA have been found to trigger different biological effects, with exon 9 and exon 20 mutations being particularly relevant. Studies have shown that concomitant mutations in both exons 9 and 20 synergistically enhance tumorigenic effects, leading to aggressive tumor behavior and poor prognosis in CRC patients. The frequency of PIK3CA mutations in CRC patients varies across different populations, with mutation rates ranging from 13.01% to 22.8%. PIK3CA mutations have been associated with higher microsatellite instability and better overall survival and progression-free survival rates in CRC patients. However, further studies with larger sample sizes and longer follow-up periods are needed to provide more robust evidence on the role of PIK3CA mutations in CRC development and prognosis.
What is GSK3beta in alzheimer?1 answersGSK3beta is a protein kinase that plays a crucial role in Alzheimer's disease (AD) by being involved in the regulation of neuropathological hallmarks such as neurofibrillary tangles and senile plaques. It is implicated in the formation of paired helical filament (PHF)-tau, which is a marker of neurodegeneration in AD. Abnormally elevated levels of GSK3beta activity have been reported in AD as well as in other neurodegenerative diseases like Parkinson's and Huntington's diseases. GSK3beta is activated by amyloid-beta (Abeta) and induces hyperphosphorylation of tau, NFT formation, neuronal death, and synaptic loss. Inhibition of GSK3beta may be beneficial in the treatment of AD. The understanding of GSK3beta is critical to the pathophysiology of AD, particularly in relation to microtubule stability and the phosphorylation of tau.