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Sci. Signal., 25 September 2012
Vol. 5, Issue 243, p. ra70
PTEN Goes Traveling
The tumor suppressor protein and phosphatase PTEN antagonizes the kinase PI3K, resulting in inhibition of the kinase Akt downstream of PI3K and reduced cellular proliferation. Mutations in PTEN are found in many different tumors. PTEN functions at the cytosolic side of the plasma membrane and in the nucleus, but Putz et al. extend its sphere of influence by showing that it can be secreted from cells in exosomes and taken up by recipient cells, where its functional activity is intact. PTEN-deficient cells that received exosomes bearing PTEN exhibited Akt inhibition and reduced proliferation. Secretion of PTEN from cells required components of the Nedd4 ubiquitination system. Given the role of PTEN in tumor suppression, these results suggest that the delivery of PTEN to tumor cells may provide an effective therapeutic strategy.
Citation: U. Putz, J. Howitt, A. Doan, C.-P. Goh, L.-H. Low, J. Silke, S.-S. Tan, The Tumor Suppressor PTEN Is Exported in Exosomes and Has Phosphatase Activity in Recipient Cells. Sci. Signal.5, ra70 (2012).
Benjamin D. Hopkins, Barry Fine, Nicole Steinbach, Meaghan Dendy, Zachary Rapp, Jacquelyn Shaw, Kyrie Pappas, Jennifer S. Yu, Cindy Hodakoski, Sarah Mense, Joshua Klein, Sarah Pegno, Maria-Luisa Sulis, Hannah Goldstein, Benjamin Amendolara, Liang Lei, Matthew Maurer, Jeffrey Bruce, Peter Canoll, Hanina Hibshoosh, and Ramon Parsons (26 July 2013) Science341 (6144), 399.
[DOI: 10.1126/science.1234907] |Abstract »|Full Text »|PDF »|Supplementary Materials »
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