Phosphatase and tensin homolog (PTEN) is a key tumor suppressor that it is mutated in multiple cancer types and antagonizes signaling through the phosphoinositide 3-kinase (PI3K) pathway. A recent study identifies a new secreted variant of PTEN that might have therapeutic utility for cancer (Science http://dx.doi.org/10.1126/science.1234907).

Benjamin Hopkins et al. found an alternative translation start site in the PTEN transcript and showed that this PTEN variant was translated when expressed in cells. Compared with classical PTEN, the alternative PTEN protein (PTEN-Long) had an additional 173 amino acids at its N terminus. The authors detected both forms of PTEN in various human cell lines, including cancer cell lines, but not in those that lacked PTEN. In primary breast tumor tissues, PTEN-Long expression was reduced in the tumors but was higher in the tumor microenvironment than in the tumor or in normal breast tissue.

The researchers then showed that PTEN-Long could be secreted and was present in human plasma and serum. Applied as an exogenous agent, PTEN-Long could block PI3K signaling in cultured cells and was able to regress tumor growth when injected into a number of different mouse xenograft tumor models.

Although further examination of the functions of this alternative PTEN variant is required, the identification of this secreted protein may allow the design of new strategies to restore PTEN to tumor cells.