The Cover

Phospholipids and lipid second messengers are important mediators of mitogenic signal transduction, but their involvement in oncogenesis and their potential as anticancer drug targets are scarcely studied. A role for phospholipases in the previously described antisignaling properties of the antitumor agent, SC-{alpha}{alpha}{delta}9, was investigated based on a hypothesis developed from molecular modeling studies, which suggested significant structural similarity between SC-{alpha}{alpha}{delta}9 (shown in yellow) and the model phospholipid, phosphatidic acid (shown in atom-specific colors). In support of this hypothesis, SC-{alpha}{alpha}{delta}9 was found to selectively inhibit phospholipase C (PLC) but not phospholipase D (PLD), and to cause a reduction in the activation of extracellular signal-regulated kinase (Erk) by oncogenic Ras. Modifications in one of the hydrophobic side chains were sufficient to abolish PLC inhibitory activity. For details, see Vogt et al. in this issue.