GSK3-beta as a candidate therapeutic target in soft tissue sarcomas

Abstract Soft tissue sarcoma (STS) is a predominantly fatal rare malignancy with inadequate treatment options. Glycogen synthase kinase 3β (GSK-3β) is an emerging target in human malignancies. Its therapeutic relevance in STS is unknown. We analyzed the prognostic impact of GSK-3β gene and protein e...

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Autores principales:	S. Verbeke, R. Perret, V. Chaire, E. Richard, V. Velasco, F. Giles, L. Cavalcante, A. Italiano
Formato:	article
Lenguaje:	EN
Publicado:	BMC 2021
Materias:	Glycogen synthase kinase 3β Soft tissue sarcomas 9-ING-41 Diseases of the blood and blood-forming organs RC633-647.5 Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/cbb98c95e2e745d88a7d6d2402a0a230
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spelling	oai:doaj.org-article:cbb98c95e2e745d88a7d6d2402a0a2302021-12-05T12:03:29ZGSK3-beta as a candidate therapeutic target in soft tissue sarcomas10.1186/s13045-021-01215-x1756-8722https://doaj.org/article/cbb98c95e2e745d88a7d6d2402a0a2302021-12-01T00:00:00Zhttps://doi.org/10.1186/s13045-021-01215-xhttps://doaj.org/toc/1756-8722Abstract Soft tissue sarcoma (STS) is a predominantly fatal rare malignancy with inadequate treatment options. Glycogen synthase kinase 3β (GSK-3β) is an emerging target in human malignancies. Its therapeutic relevance in STS is unknown. We analyzed the prognostic impact of GSK-3β gene and protein expression in two independent cohorts of patients with STS. We then treated STS cell lines and mice xenografts with a novel GSK-3 inhibitor 9-ING-41 alone or in combination with chemotherapy. We demonstrated that 9-ING-41 treatment induced significant STS cells apoptosis and was synergistic in vivo when combined with chemotherapy. Mechanistically, 9-ING-41 induces significant apoptosis of STS cells via suppression of NF-κB-mediated X-linked inhibitor of apoptosis protein (XIAP) expression. These data support the inclusion of patients with STS in clinical studies of 9-ING-41 alone and in combination with chemotherapy.S. VerbekeR. PerretV. ChaireE. RichardV. VelascoF. GilesL. CavalcanteA. ItalianoBMCarticleGlycogen synthase kinase 3βSoft tissue sarcomas9-ING-41Diseases of the blood and blood-forming organsRC633-647.5Neoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENJournal of Hematology & Oncology, Vol 14, Iss 1, Pp 1-5 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Glycogen synthase kinase 3β Soft tissue sarcomas 9-ING-41 Diseases of the blood and blood-forming organs RC633-647.5 Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	Glycogen synthase kinase 3β Soft tissue sarcomas 9-ING-41 Diseases of the blood and blood-forming organs RC633-647.5 Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 S. Verbeke R. Perret V. Chaire E. Richard V. Velasco F. Giles L. Cavalcante A. Italiano GSK3-beta as a candidate therapeutic target in soft tissue sarcomas
description	Abstract Soft tissue sarcoma (STS) is a predominantly fatal rare malignancy with inadequate treatment options. Glycogen synthase kinase 3β (GSK-3β) is an emerging target in human malignancies. Its therapeutic relevance in STS is unknown. We analyzed the prognostic impact of GSK-3β gene and protein expression in two independent cohorts of patients with STS. We then treated STS cell lines and mice xenografts with a novel GSK-3 inhibitor 9-ING-41 alone or in combination with chemotherapy. We demonstrated that 9-ING-41 treatment induced significant STS cells apoptosis and was synergistic in vivo when combined with chemotherapy. Mechanistically, 9-ING-41 induces significant apoptosis of STS cells via suppression of NF-κB-mediated X-linked inhibitor of apoptosis protein (XIAP) expression. These data support the inclusion of patients with STS in clinical studies of 9-ING-41 alone and in combination with chemotherapy.
format	article
author	S. Verbeke R. Perret V. Chaire E. Richard V. Velasco F. Giles L. Cavalcante A. Italiano
author_facet	S. Verbeke R. Perret V. Chaire E. Richard V. Velasco F. Giles L. Cavalcante A. Italiano
author_sort	S. Verbeke
title	GSK3-beta as a candidate therapeutic target in soft tissue sarcomas
title_short	GSK3-beta as a candidate therapeutic target in soft tissue sarcomas
title_full	GSK3-beta as a candidate therapeutic target in soft tissue sarcomas
title_fullStr	GSK3-beta as a candidate therapeutic target in soft tissue sarcomas
title_full_unstemmed	GSK3-beta as a candidate therapeutic target in soft tissue sarcomas
title_sort	gsk3-beta as a candidate therapeutic target in soft tissue sarcomas
publisher	BMC
publishDate	2021
url	https://doaj.org/article/cbb98c95e2e745d88a7d6d2402a0a230
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GSK3-beta as a candidate therapeutic target in soft tissue sarcomas

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