Regulation and modulation of PTEN activity

Abstract

PTEN (Phosphatase and tensin homolog deleted on chromosome ten) is a tumor suppressor that is frequently mutated in most human cancers. PTEN is a lipid and protein phosphatase that antagonizes PI3K/AKT pathway through lipid phosphatase activity at the plasma membrane. More recent studies showed that, in addition to the putative role of PTEN as a PI(3,4,5)P3 3-phosphatase, it is a PI(3,4)P2 3-phosphatase during stimulation of class I PI3K signaling pathway by growth factor. Although PTEN tumor suppressor function via it's lipid phosphatase activity occurs primarily in the plasma membrane, it can also be found in the nucleus, in cytoplasmic organelles and extracellular space. PTEN has also shown phosphatase independent functions in the nucleus. PTEN can exit from the cell through exosomal export or secretion and has a tumor suppressor function in adjacent cells. PTEN has a critical role in growth, the cell cycle, protein synthesis, survival, DNA repair and migration. Understanding the regulation of PTEN function, activity, stability, localization and its dysregulation outcomes and also the intracellular and extracellular role of PTEN and paracrine role of PTEN-L in tumor cells as an exogenous therapeutic agent can help to improve clinical conceptualization and treatment of cancer.

RETRACTED ARTICLE: Roles of the PI3K/AKT/mTOR signalling pathways in neurodegenerative diseases and tumours

“…The tumour suppressor PTEN catalyses the reaction opposite of PIP3 generation by converting PIP3 to PIP2 [66,67]. PTEN downregulates the PI3K/AKT/mTOR pathway to suppress cell proliferation and interfere with cellular metabolism, and inhibition of PTEN activity activates AKT and downstream pathways [68]. PTEN-knockout mice died during development due to the abnormal proliferation of various tissues.…”

Transcriptomic Analysis of Cellular Pathways in Healing Flexor Tendons of Plasminogen Activator Inhibitor 1 (PAI‐1/Serpine1) Null Mice

“…PTEN is a ubiquitous negative regulator of the PI3K/Akt/mTOR and MAPK signaling pathways . Mutations in the PTEN gene can lead to a spectrum of rare disorders known as the PTEN hamartoma tumor syndrome (PHTS) and have also been associated with multiple cancers . It was recently shown that TGF‐β1‐induced suppression of PTEN signaling pathway leads to fibrosis in human tenon's fibroblasts .…”

“…14 Mutations in the PTEN gene can lead to a spectrum of rare disorders known as the PTEN hamartoma tumor syndrome (PHTS) 15 and have also been associated with multiple cancers. 16 It was recently shown that TGF-β1-induced suppression of PTEN signaling pathway leads to fibrosis in human tenon's fibroblasts. 17 Analysis of alveolar epithelial cells from idiopathic pulmonary fibrosis patients also linked the activation of nuclear factor-κB with reduced PTEN levels and both were associated with senescence, which is likely an initiating insult in lung fibrosis.…”

Head and neck cancer during pregnancy

“…The inactivation of pRb will dysregulate the cell division cycle and induce S-phase reentry in postmitotic, differentiated cells. 82 Upregulation of Bcl-2 promotes cellular survival and inhibits the actions of proapoptotic proteins. 81 Downregulation of PTEN, a tumor gene suppressor, activates cell survival, growth, and proliferation.…”

“…81 Downregulation of PTEN, a tumor gene suppressor, activates cell survival, growth, and proliferation. 82 Upregulation of Bcl-2 promotes cellular survival and inhibits the actions of proapoptotic proteins. Clinical studies studied in vivo the implication of estrogen in HPV-related carcinogenesis.…”