2.2.7 Sphingosine-1-phosphate receptor 2 (S1PR2)
In diffuse large B-cell lymphoma (DLBCL), the sphingosine-1-phosphate receptor S1PR2 and its downstream signaling pathway are absent and repressed by the transcription factor FOXP1. Anna Stelling et al 48 found that the TGF-β/TGF-βR2/SMAD1 axis was involved in the transcriptional activation of S1PR2. There was a positive trend between SMAD1 and TGF-βR2 and S1PR2 expression, and TGF-β signaling controlled S1PR2 expression through TGF-βR2 and SMAD1. S1PR2-deficient SU-DHL-6 clones failed to undergo apoptosis upon exposure to TGF-β, suggesting that S1PR2 played a key role in TGF-β-driven apoptosis. In CRISPR-mediated DLBCL cell lines, gene editing of any of S1PR2, SMAD1, and TGFBR2 rendered tumor cells unresponsive to apoptosis by means of TGF-β. S1PR2 is an important transcription factor, and its deletion can cause over-proliferation of the developmental center (GC) B cell chamber and also affect the adhesion process of B cells and T cells accordingly promoting the formation of lymphoma.