The PTEN⁻PI3K Axis in Cancer

Biomolecules. 2019 Apr 17;9(4):153. doi: 10.3390/biom9040153.


The PI3K-AKT-mTOR signal transduction pathway regulates a variety of biological processes including cell growth, cell cycle progression and proliferation, cellular metabolism, and cytoskeleton reorganization. Fine-tuning of the phosphatidylinositol 3-kinase (PI3K) pathway signaling output is essential for the maintenance of tissue homeostasis and uncontrolled activation of this cascade leads to a number of human pathologies including cancer. Inactivation of the tumor suppressor phosphatase and tensin homologue deleted on Chromosome 10 (PTEN) and/or activating mutations in the proto-typical lipid kinase PI3K have emerged as some of the most frequent events associated with human cancer and as a result the PI3K pathway has become a highly sought-after target for cancer therapies. In this review we summarize the essential role of the PTEN-PI3K axis in controlling cellular behaviors by modulating activation of key proto-oncogenic molecular nodes and functional targets. Further, we highlight important functional redundancies and peculiarities of these two critical enzymes that over the last few decades have become a central part of the cancer research field and have instructed hundreds of pre-clinical and clinical trials to better cancer treatments.

Keywords: PI3K; PTEN; cancer predisposition syndromes; mouse models of human cancer; targeted therapies.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Humans
  • Neoplasms / metabolism*
  • PTEN Phosphohydrolase / genetics
  • PTEN Phosphohydrolase / metabolism*
  • Phosphatidylinositol 3-Kinases / genetics
  • Phosphatidylinositol 3-Kinases / metabolism*
  • Signal Transduction


  • PTEN Phosphohydrolase