New insights into tumor suppression: PTEN suppresses tumor formation by restraining the phosphoinositide 3-kinase/AKT pathway

Lewis C. Cantley*,†,‡ and
Benjamin G. Neel§

^*Department of Cell Biology, Harvard Medical School, Boston, MA 02115; ^†Division of Signal Transduction, Department of Medicine; Beth Israel Deaconess Medical Center, Boston, MA 02215; and ^§Cancer Biology Program, Division of Hematology-Oncology, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA 02215

Abstract

The most recently discovered PTEN tumor suppressor gene has been found to be defective in a large number of human cancers. In addition, germ-line mutations in PTEN result in the dominantly inherited disease Cowden syndrome, which is characterized by multiple hamartomas and a high proclivity for developing cancer. A series of publications over the past year now suggest a mechanism by which PTEN loss of function results in tumors. PTEN appears to negatively control the phosphoinositide 3-kinase signaling pathway for regulation of cell growth and survival by dephosphorylating the 3 position of phosphoinositides.

Footnotes

↵ ‡ To whom reprint requests should be addressed at: Harvard Institutes of Medicine, 77 Avenue Louis Pasteur, Room 1024, Boston, MA 02115. e-mail: cantley{at}helix.mgh.harvard.edu.
ABBREVIATIONS:

PI3K,

phosphoinositide 3-kinase;

PTP,

protein-tyrosine phosphatase;

PtdIns,

phosphatidylinositol;

PH domain,

pleckstrin homology domain;

PDGF,

platelet-derived growth factor;

GSK3,

glycogen synthase kinase 3