Pezcoller Foundation-AACR International Award for Cance...( hemical structural and dynamic bases f...),Health

Cantley continued to focus on the biochemical basis for the mechanism and regulation of membrane-associated enzymes as an assistant professor in the biochemistry and molecular biology department at Harvard University.

From there, Cantley joined the physiology faculty of Tufts University School of Medicine where, with colleagues, he examined the biochemical mechanisms of cellular response to oncogenes and growth factors. It was during this time that his laboratory discovered phosphoinositide 3-kinase (PI3K), an enzyme that puts a phosphate group on the membrane lipid phosphatidylinositol. Although prior work in the 1950s had shown that phosphatidylinositol was phosphorylated in human tissues, Cantley's laboratory discovered an enzyme that could phosphorylate a unique position on phosphatidylinositol (the 3 position of the inositol moiety), revealing a new lipid not previously known to exist in nature. More importantly, this lipid was produced only when cells were stimulated with growth factors or made cancerous with oncogenes. In addition, genetic evidence indicated that activation of PI3K by oncogenes was a critical event in transforming a normal cell to a cancerous cell.

In 1992, Cantley moved to Harvard Medical School and Beth Israel Deaconess Hospital, where he and his team further explored the PI3K pathway. They postulated that the novel membrane lipid made by PI3K might act as an intracellular "messenger" by recruiting to the cell membrane the machinery (signaling proteins) needed to communicate a growth signal to the cell. Continuous activation of PI3K would allow the cell to continually grow and make copies of itself, resulting in a cancerous tumor. Research over the past decade by numerous laboratories has supported this model and provided evidence that PI3K plays a critical role in many human cancers.

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Contact: Elizabeth J. Tait
Tait@aacr.org
215-440-9300
American Association for Cancer Research
4-Apr-2005