TY - JOUR
T1 - Calcineurin-independent NFATc1 signaling is essential for survival of Burkitt lymphoma cells
AU - Murti, Krisna
AU - Fender, Hendrik
AU - Glatzle, Carolin
AU - Wismer, Rhoda
AU - Sampere-Birlanga, Salvador
AU - Wild, Vanessa
AU - Muhammad, Khalid
AU - Rosenwald, Andreas
AU - Serfling, Edgar
AU - Avots, Andris
N1 - Publisher Copyright:
Copyright © 2023 Murti, Fender, Glatzle, Wismer, Sampere-Birlanga, Wild, Muhammad, Rosenwald, Serfling and Avots.
PY - 2023
Y1 - 2023
N2 - 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-κB 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.
AB - 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-κB 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.
KW - activated B cell-like diffuse large B-cell lymphoma (ABC-DLBCL)
KW - apoptosis
KW - B cell receptor (BCR)
KW - Burkitt lymphoma
KW - Burkitt lymphoma (BL)
KW - cyclosporin A
KW - NFATc1
KW - nuclear localization
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UR - http://www.scopus.com/inward/citedby.url?scp=85167349276&partnerID=8YFLogxK
U2 - 10.3389/fonc.2023.1205788
DO - 10.3389/fonc.2023.1205788
M3 - Article
AN - SCOPUS:85167349276
SN - 2234-943X
VL - 13
JO - Frontiers in Oncology
JF - Frontiers in Oncology
M1 - 1205788
ER -
