CANCER

Turning the tables on an inhibitor

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Science  03 Apr 2015:
Vol. 348, Issue 6230, pp. 87-88
DOI: 10.1126/science.348.6230.87-p

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

Sci. Signal. 8, ra32 (2015).

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