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A Secreted PTEN Phosphatase that Enters Cells to Alter Signaling and Survival

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Science  06 Jun 2013:
1234907
DOI: 10.1126/science.1234907

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Abstract

Phosphatase and Tensin Homolog on chromosome Ten (PTEN) is a tumor suppressor and an antagonist of the phosphoinositide-3 kinase (PI3K) pathway. We identified a 576-amino acid translational variant of PTEN, termed PTEN-Long, that arises from an alternative translation start site 519 bp upstream of the ATG initiation sequence, adding 173 N-terminal amino acids to the normal PTEN open reading frame. PTEN-Long is a membrane permeable lipid phosphatase that is secreted from cells and can enter other cells. As an exogenous agent, PTEN-Long antagonized PI3K signaling and induced tumor cell death in vitro and in vivo. By providing a means to restore a functional tumor suppressor protein to tumor cells, PTEN-Long may have therapeutic uses.

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