Tumor suppressor PTEN: modulator of cell signaling, growth, migration and apoptosis

Abstract

PTEN (also known as MMAC-1 or TEP-1) is one of the most frequently mutated tumor suppressors in human cancer. It is also essential for embryonic development. PTEN functions primarily as a lipid phosphatase to regulate crucial signal transduction pathways; a key target is phosphatidylinositol 3,4,5-trisphosphate. In addition, it displays weak tyrosine phosphatase activity, which may downmodulate signaling pathways that involve focal adhesion kinase (FAK) or Shc. Levels of PTEN are regulated in embryos and adult organisms, and gene-targeting studies demonstrate that it has a crucial role in normal development. Functions for PTEN have been identified in the regulation of many normal cell processes, including growth, adhesion, migration, invasion and apoptosis. PTEN appears to play particularly important roles in regulating anoikis (apoptosis of cells after loss of contact with extracellular matrix) and cell migration. Gene targeting and transient expression studies have provided insight into the specific signaling pathways that regulate these processes. Characterization of the diverse signaling networks modulated by PTEN, as well as the regulation of PTEN concentration, enzymatic activity, and coordination with other phosphatases, should provide intriguing new insight into the biology of normal and malignant cells.

Mechanochemical feedback underlies coexistence of qualitatively distinct cell polarity patterns within diverse cell populations

“…For instance, the transition to invasive, vertical growth in melanoma is accompanied by a range of mutations, some of which can directly drive invasion (e.g., mutations in integrins) or alter ECM (e.g., mutations affecting matrix metalloproteinases) (26)(27)(28)(29). The role of other mutations is less clear; for example, although the loss of phosphatase and tensin homolog (PTEN) is frequently correlated with enhanced melanoma invasiveness (30,31), the exact nature of how the corresponding change in the signaling network activity might affect invasive cell migration is not known.…”

Myeloid PTEN deficiency aggravates renal inflammation and fibrosis in angiotensin II‐induced hypertension

“…PTEN is originally identified as a tumor suppressor (Li et al, 1997; Simpson & Parsons, 2001). Subsequent studies have shown that PTEN plays a vital role in regulating cell growth and survival through the phosphatidylinositol 3 kinase (PI3K)/AKT signaling pathway (Leslie & Downes, 2002; Song et al, 2012; Yamada & Araki, 2001). Recently, we have demonstrated that PI3 Kinase γ deficiency decreased kidney injury and fibrosis in AngII‐induced hypertension (An et al, 2020).…”

Role of MicroRNAs in Signaling Pathways Associated with the Pathogenesis of Idiopathic Pulmonary Fibrosis: A Focus on Epithelial-Mesenchymal Transition

“…In this case, Akt phosphorylates and inactivates the expression of Forkhead Box O3 (FoxO3), a target gene of Akt in PI3K/Akt signaling pathway, and whose main function is to inhibit the cell cycle and to promote apoptosis [ 68 , 105 ]. On the other hand, PTEN, which has a critical role in regulating fibroblast removal during tissue repair, is considered the major negative regulator of the PI3K/Akt signal pathway, by inhibiting the Akt phosphorylation and promoting fibroblast apoptosis during tissue repair [ 106 , 107 ]. It has been described also that the regulation of expression genes involved with cell survival is regulated by p65, a subunit of NF-kβ, when Akt promotes its activation.…”