Recent advances in PTEN signalling axes in cancer

In over two decades since the discovery of phosphatase and tensin homologue deleted on chromosome 10 (PTEN), nearly 18,000 publications have attempted to elucidate its functions and roles in normal physiology and disease. The frequent disruption of PTEN in cancer cells was a strong indication that it had critical roles in tumour suppression. Germline PTEN mutations have been identified in patients with heterogeneous tumour syndromic diseases, known as PTEN hamartoma tumour syndrome (PHTS), and in some individuals with autism spectrum disorders (ASD). Today we know that by limiting oncogenic signalling through the phosphoinositide 3-kinase (PI3K) pathway, PTEN governs a number of processes including survival, proliferation, energy metabolism, and cellular architecture. Some of the most exciting recent advances in the understanding of PTEN biology and signalling have revisited its unappreciated roles as a protein phosphatase, identified non-enzymatic scaffold functions, and unravelled its nuclear function. These discoveries are certain to provide a new perspective on its full tumour suppressor potential, and knowledge from this work will lead to new anti-cancer strategies that exploit PTEN biology. In this review, we will highlight some outstanding questions and some of the very latest advances in the understanding of the tumour suppressor PTEN.