Targeting sphingosine kinase by ABC294640 induces KSHV-infected endothelial cell autophagic death. Homo sapiens

KSHV is a principal causative agent of Kaposi's Sarcoma (KS). Despite this knowledge about the close relationship between sphingolipid metablism and solid tumors development, the role of sphingolipid metablism in KSHV-related malignancies remains mostly unclear. We report that targeting sphingosine kinase 2 (SphK2) by a selective inhibitor, ABC294640, significantly induces KSHV+ TIVE-LTC autophagic death. By using microarray analysis, we have identified the global gene profile affected by ABC294640 within KSHV+ TIVE-LTC and several novel “druggable” candidates closely related to cancer cell survival/growth. Finally, we found that targeting TIVE-LTC by ABC294640 effectively suppressed KSHV tumorigenicity by using a KS-like nude mice model. Overall design: TIVE-LTC were treated with vehicle control or SphK2 inhibitor ABC294640 (60 µM) for 24 h, and the gene expression signature was compared to respective vehicle controls