| First Author | Malek M | Year | 2017 |
| Journal | Mol Cell | Volume | 68 |
| Issue | 3 | Pages | 566-580.e10 |
| PubMed ID | 29056325 | Mgi Jnum | J:251968 |
| Mgi Id | MGI:6106849 | Doi | 10.1016/j.molcel.2017.09.024 |
| Citation | Malek M, et al. (2017) PTEN Regulates PI(3,4)P2 Signaling Downstream of Class I PI3K. Mol Cell 68(3):566-580.e10 |
| abstractText | The PI3K signaling pathway regulates cell growth and movement and is heavily mutated in cancer. Class I PI3Ks synthesize the lipid messenger PI(3,4,5)P3. PI(3,4,5)P3 can be dephosphorylated by 3- or 5-phosphatases, the latter producing PI(3,4)P2. The PTEN tumor suppressor is thought to function primarily as a PI(3,4,5)P3 3-phosphatase, limiting activation of this pathway. Here we show that PTEN also functions as a PI(3,4)P2 3-phosphatase, both in vitro and in vivo. PTEN is a major PI(3,4)P2 phosphatase in Mcf10a cytosol, and loss of PTEN and INPP4B, a known PI(3,4)P2 4-phosphatase, leads to synergistic accumulation of PI(3,4)P2, which correlated with increased invadopodia in epidermal growth factor (EGF)-stimulated cells. PTEN deletion increased PI(3,4)P2 levels in a mouse model of prostate cancer, and it inversely correlated with PI(3,4)P2 levels across several EGF-stimulated prostate and breast cancer lines. These results point to a role for PI(3,4)P2 in the phenotype caused by loss-of-function mutations or deletions in PTEN. |
