The PTEN⁻PI3K Axis in Cancer

Antonella Papa, Pier Paolo Pandolfi

Research output: Contribution to journalReview ArticleResearchpeer-review

6 Citations (Scopus)

Abstract

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.

Original languageEnglish
Article number153
Number of pages11
JournalBiomolecules
Volume9
Issue number4
DOIs
Publication statusPublished - 17 Apr 2019

Keywords

  • cancer predisposition syndromes
  • mouse models of human cancer
  • PI3K
  • PTEN
  • targeted therapies

Cite this

Papa, Antonella ; Pandolfi, Pier Paolo. / The PTEN⁻PI3K Axis in Cancer. In: Biomolecules. 2019 ; Vol. 9, No. 4.
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The PTEN⁻PI3K Axis in Cancer. / Papa, Antonella; Pandolfi, Pier Paolo.

In: Biomolecules, Vol. 9, No. 4, 153, 17.04.2019.

Research output: Contribution to journalReview ArticleResearchpeer-review

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AU - Pandolfi, Pier Paolo

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AB - 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.

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