Frontiers in Oncology (Jul 2023)

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

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

DOI
https://doi.org/10.3389/fonc.2023.1205788
Journal volume & issue
Vol. 13

Abstract

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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.

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