Research ArticleCancer

PTEN inhibits PREX2-catalyzed activation of RAC1 to restrain tumor cell invasion

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Science Signaling  31 Mar 2015:
Vol. 8, Issue 370, pp. ra32
DOI: 10.1126/scisignal.2005840

Turning the tables on an inhibitor

Loss-of-function mutations are commonly detected in the tumor suppressor PTEN in various cancers. The lipid phosphatase activity of PTEN inhibits cell proliferation. In cancer, enhanced cell proliferation and migration often go hand in hand. Indeed, PTEN is inhibited by PREX2, a protein that promotes cell migration. Mense et al. found that the inhibition was reciprocal: Independently from its lipid phosphatase activity, PTEN suppressed the activity of PREX2. Forms of PREX2 with cancer-associated mutations were not inhibited by PTEN, inhibited the lipid phosphatase activity of PTEN, and promoted cancer cell invasion. Analysis of human tumors revealed a correlation between PREX2 mutation and high PTEN expression, suggesting that tumors select for PREX2 mutants with attenuated PTEN inhibition.