Neutral Sphingomyelinases in Cancer: Friend or Foe?

For many years, neutral sphingomyelinases (N-SMases) were long thought to be anticancer enzymes owing to their roles as key producers of ceramide linked to apoptosis, growth arrest, and the chemotherapeutic response. However, in recent years, with the cloning of multiple isoforms and with new information on their cellular roles, particularly for nSMase2, a more complex picture is emerging suggesting that N-SMases have both pro- and anticancer roles. In this chapter, we will summarize current knowledge on N-SMase expression in cancer and the roles of N-SMase activity and specific isoforms in cancer-relevant biologies. We will also discuss what we see as the major challenges ahead for research into N-SMases in cancer.