Cholesterol plays a role in the regulation of cell signaling mechanisms in cancer.
In a publication selected as a Highlight of the July 1 issue of Cancer Research, Adam et al. demonstrate that cholesterol-rich, lipid raft microdomains regulate signaling to the serine-threonine kinase Akt. These workers describe a lipid raft-resident subpopulation of endogenous Akt1 with markedly greater cholesterol sensitivity compared to Akt1 elsewhere in cells. Myristoylated Akt1 (MyrAkt1), a potent oncogene, localized preferentially to raft membranes, exhibited distinct substrate preferences compared to MyrAkt1 in non-raft fractions, and conferred cholesterol-dependent protection from apoptosis. These findings indicate that cholesterol regulates signal transduction by direct effects on Akt and that oncogenic consequences of myristoylation arise, in part, because MyrAkt1 is enriched in cholesterol-rich membranes.

Fang et al. demonstrate a role for caveolin in development. Cover article in the December issue of American Journal of Pathology.