Calcineurin-independent NFATc1 signaling is essential for survival of Burkitt lymphoma cells.

Autor:	Murti K; Department of Molecular Pathology, Institute of Pathology, and Comprehensive Cancer Center Mainfranken, Julius-Maximilians University of Wuerzburg, Wuerzburg, Germany., Fender H; Department of Molecular Pathology, Institute of Pathology, and Comprehensive Cancer Center Mainfranken, Julius-Maximilians University of Wuerzburg, Wuerzburg, Germany., Glatzle C; Department of Molecular Pathology, Institute of Pathology, and Comprehensive Cancer Center Mainfranken, Julius-Maximilians University of Wuerzburg, Wuerzburg, Germany., Wismer R; Department of Molecular Pathology, Institute of Pathology, and Comprehensive Cancer Center Mainfranken, Julius-Maximilians University of Wuerzburg, Wuerzburg, Germany., Sampere-Birlanga S; Department of Molecular Pathology, Institute of Pathology, and Comprehensive Cancer Center Mainfranken, Julius-Maximilians University of Wuerzburg, Wuerzburg, Germany., Wild V; Department of Molecular Pathology, Institute of Pathology, and Comprehensive Cancer Center Mainfranken, Julius-Maximilians University of Wuerzburg, Wuerzburg, Germany., Muhammad K; Department of Molecular Pathology, Institute of Pathology, and Comprehensive Cancer Center Mainfranken, Julius-Maximilians University of Wuerzburg, Wuerzburg, Germany., Rosenwald A; Department of Molecular Pathology, Institute of Pathology, and Comprehensive Cancer Center Mainfranken, Julius-Maximilians University of Wuerzburg, Wuerzburg, Germany., Serfling E; Department of Molecular Pathology, Institute of Pathology, and Comprehensive Cancer Center Mainfranken, Julius-Maximilians University of Wuerzburg, Wuerzburg, Germany., Avots A; Department of Molecular Pathology, Institute of Pathology, and Comprehensive Cancer Center Mainfranken, Julius-Maximilians University of Wuerzburg, Wuerzburg, Germany.
Jazyk:	angličtina
Zdroj:	Frontiers in oncology [Front Oncol] 2023 Jul 21; Vol. 13, pp. 1205788. Date of Electronic Publication: 2023 Jul 21 (Print Publication: 2023).
DOI:	10.3389/fonc.2023.1205788
Abstrakt:	In Burkitt lymphoma (BL), a tumor of germinal center B cells, the pro-apoptotic properties of MYC are controlled by tonic B cell receptor (BCR) signals. Since BL cells do not exhibit constitutive NF- κ B activity, we hypothesized that anti-apoptotic NFATc1 proteins provide a major transcriptional survival signal in BL. Here we show that post-transcriptional mechanisms are responsible for the calcineurin (CN) independent constitutive nuclear over-expression of NFATc1 in BL and Eµ-MYC - induced B cell lymphomas (BCL). Conditional inactivation of the Nfatc1 gene in B cells of Eµ-MYC mice leads to apoptosis of BCL cells in vivo and ex vivo . Inhibition of BCR/SYK/BTK/PI3K signals in BL cells results in cytosolic re-location of NFATc1 and apoptosis. Therefore, NFATc1 activity is an integrated part of tonic BCR signaling and an alternative target for therapeutic intervention in BL. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2023 Murti, Fender, Glatzle, Wismer, Sampere-Birlanga, Wild, Muhammad, Rosenwald, Serfling and Avots.)
Databáze:	MEDLINE
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