Papa, A.; Pandolfi, P.P. The PTEN–PI3K Axis in Cancer. Biomolecules2019, 9, 153.
Papa, A.; Pandolfi, P.P. The PTEN–PI3K Axis in Cancer. Biomolecules 2019, 9, 153.
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 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 tumour suppressor phosphatase 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.
PTEN; PI3K; cancer predisposition syndromes; targeted therapies; mouse models of human cancer
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