Sphingosine kinase 1 (SK1) is a key
sphingolipid enzyme that is upregulated in several types of
cancer, including
lymphoma which is a heterogenous group of
malignancies. Treatment for
lymphoma has improved significantly by the introduction of new
therapies; however, subtypes with
tumor protein P53 (p53) mutations or deletion have poor prognosis, making it critical to explore new therapeutic strategies in this context. SK1 has been proposed as a therapeutic target in different types of
cancer; however, the effect of targeting SK1 in
cancers with p53 deletion has not been evaluated yet. Previous work from our group suggests that loss of SK1 is a key event in mediating the
tumor suppressive effect of p53. Employing both genetic and pharmacological approaches to inhibit SK1 function in Trp53KO mice, we show that targeting SK1 decreases
tumor growth of established p53KO thymic
lymphoma. Inducible deletion of Sphk1 or its pharmacological inhibition drive increased cell death in
tumors which is accompanied by selective accumulation of
sphingosine levels. These results demonstrate the relevance of SK1 in the growth and maintenance of
lymphoma in the absence of p53 function, positioning this
enzyme as a potential therapeutic target for the treatment of
tumors that lack functional p53.