Novel mechanisms of PTEN regulation

The tumour suppressor phosphatase and tensin homolog (PTEN) is one of the most important tumour suppressors. It was discovered in 1997 and since then much has been done to understand its physiological functions and how loss of PTEN function and regulation contributes to cancer. Through dephosphorylation of the lipid PtdIns(3,4,5)P3, PTEN antagonises the PI3-kinase/AKT signalling pathway, thus regulating cell growth and proliferation. PTEN functions are found altered in different sporadic tumour samples (glioblastoma, endometrial, breast, liver, prostate) and in patients suffering from inherited conditions (Cowden disease, Bannayan-Riley-Ruvalcaba syndrome and autism). The identification of new PTEN mutations and the characterization of novel PTEN functions are continually increasing. Although the majority of the mutations analysed are reported to abrogate PTEN phosphatase activity, through the characterization of a panel of PTEN mutations associated with a variety of different phenotypes (tumours and syndromes), we found that an increasing number of mutants behave differently, implying that antagonising the AKT pathway is not the only way for PTEN to regulate tumour formation and progression.