AUTHOR=Murti Krisna , Fender Hendrik , Glatzle Carolin , Wismer Rhoda , Sampere-Birlanga Salvador , Wild Vanessa , Muhammad Khalid , Rosenwald Andreas , Serfling Edgar , Avots Andris 

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

JOURNAL=Frontiers in Oncology

VOLUME=13

YEAR=2023

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2023.1205788

DOI=10.3389/fonc.2023.1205788

ISSN=2234-943X

ABSTRACT=<p>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-<italic>κ</italic>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 <italic>Eµ-MYC</italic> – induced B cell lymphomas (BCL). Conditional inactivation of the <italic>Nfatc1</italic> gene in B cells of <italic>Eµ-MYC</italic> mice leads to apoptosis of BCL cells <italic>in vivo</italic> and <italic>ex vivo</italic>. 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.</p>