Palytoxin is a novel skin
tumor promoter, which has been used to help probe the role of different types of signaling mechanisms in
carcinogenesis. The multistage mouse skin model indicates that
tumor promotion is an early, prolonged, and reversible phase of
carcinogenesis. Understanding the molecular mechanisms underlying
tumor promotion is therefore important for developing strategies to prevent and treat
cancer. Naturally occurring
tumor promoters that bind to specific cellular receptors have proven to be useful tools for investigating important biochemical events in multistage
carcinogenesis. For example, the identification of
protein kinase C as the receptor for the prototypical skin
tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) (also called
phorbol 12-
myristate 13-
acetate, PMA) provided key evidence that
tumor promotion involves the aberrant modulation of signaling cascades that govern cell fate and function. The subsequent discovery that
palytoxin, a marine toxin isolated from zoanthids (genus Palythoa), is a potent skin
tumor promoter yet does not activate
protein kinase C indicated that investigating
palytoxin action could help reveal new aspects of
tumor promotion. Interestingly, the putative receptor for
palytoxin is the Na(+),K(+)-
ATPase. This review focuses on
palytoxin-stimulated signaling and how
palytoxin has been used to investigate alternate biochemical mechanisms by which important targets in
carcinogenesis can be modulated.