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RSS FeedsIJMS, Vol. 22, Pages 11147: CHIR99021, trough GSK-3β Targeting, Reduces Epithelioid Sarcoma Cell Proliferation by Activating Mitotic Catastrophe and Autophagy (International Journal of Molecular Sciences)

 
 

15 october 2021 15:41:04

 
IJMS, Vol. 22, Pages 11147: CHIR99021, trough GSK-3β Targeting, Reduces Epithelioid Sarcoma Cell Proliferation by Activating Mitotic Catastrophe and Autophagy (International Journal of Molecular Sciences)
 


Epithelioid sarcoma (ES) is a rare disease representing <1% of soft tissue sarcomas. Current therapies are based on anthracycline alone or in combination with ifosfamide or other cytotoxic drugs. ES is still characterized by a poor prognosis with high rates of recurrence. Indeed, for years, ES survival rates have remained stagnant, suggesting that conventional treatments should be revised and improved. New therapeutic approaches are focused to target the key regulators of signaling pathways, the causative markers of tumor pathophysiology. To this end, we selected, among the drugs to which an ES cell line is highly sensitive, those that target signaling pathways known to be dysregulated in ES. In particular, we found a key role for GSK-3β, which results in up-regulation in tumor versus normal tissue samples and associated to poor prognosis in sarcoma patients. Following this evidence, we evaluated CHIR99021, a GSK-3 inhibitor, as a potential drug for use in ES therapy. Our data  highlight that, in ES cells, CHIR99021 induces cell cycle arrest, mitotic catastrophe (MC) and autophagic response, resulting in reduced cell proliferation. Our results support the potential efficacy of CHIR99021 in ES treatment and encourage further preclinical and clinical studies.


 
150 viewsCategory: Biochemistry, Biophysics, Molecular Biology
 
IJMS, Vol. 22, Pages 11146: Synergistic Action of Antimicrobial Lung Proteins against Klebsiella pneumoniae (International Journal of Molecular Sciences)
IJMS, Vol. 22, Pages 11148: The Role of MAPK3/1 and AKT in the Acquisition of High Meiotic and Developmental Competence of Porcine Oocytes Cultured In Vitro in FLI Medium (International Journal of Molecular Sciences)
 
 
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