The Role of PTEN in Epithelial–Mesenchymal Transition

Abstract

Phosphatase and Tensin Homolog deleted on Chromosome 10 (PTEN) is one of the critical tumor suppressor genes and the main negative regulator of the PI3K pathway. PTEN is frequently found to be inactivated, either partially or fully, in various malignancies. The PI3K/AKT pathway is considered to be one of the main signaling cues that drives the proliferation of cells. Perhaps it is not surprising, then, that this pathway is hyperactivated in highly proliferative tumors. Importantly, the PI3K/AKT pathway also coordinates the epithelial–mesenchymal transition (EMT), which is pivotal for the initiation of metastases and hence is regarded as an attractive target for the treatment of metastatic cancer. It was shown that PTEN suppresses EMT, although the exact mechanism of this effect is still not fully understood. This review is an attempt to systematize the published information on the role of PTEN in the development of malignant tumors, with a main focus on the regulation of the PI3K/AKT pathway in EMT.

Primary Cilia Restrain PI3K-AKT Signaling to Orchestrate Human Decidualization

“…PTEN is the main negative regulator of the PI3K pathway and participates in multi-cilia formation and cilia disassembly [ 29 , 41 ]. Primary cilia loss causes destabilization of PTEN and activation of AKT [ 42 ].…”

“…Inhibition of Aurora A in stromal cells also down-regulates AKT phosphorylation in our study. PTEN is a negative regulator of AKT activation [ 29 , 41 ]. In human endometrium, PTEN protein level is increased by progesterone [ 59 ].…”

METTL3-m6A methylation inhibits Type II Alveolar Epithelial Cells proliferation and viability by promoting PTEN mRNA stability and translation efficiency in the acute lung injury

“…All culture media contained 100 mg/ml streptomycin and 100 U/ml penicillin. Next, AECII were incubated with LPS at different concentrations (5,10,20,25, or 50 mg/mL) for 12 h in a cell culture incubator in the atmosphere of 95% air and 5% CO 2 at 37 ˚C.…”

“…Cell counting kit-8 analysis AECII were seeded into 96-well plates (Corning Inc., Corning, NY, USA) at a density of 2 × 10 4 cells per well in three copies for each testing condition. The next day, the cells were incubated with vehicle or LPS (Sigma) at different concentrations (5,10,25, or 50 μM) and cultured in the atmosphere of 95% air and 5% CO 2 at 37 °C for ~24 h. On the third day, 10 μL of the cell counting kit-8 (CCK-8; Vazyme Biotech, Nanjing, China) reagent was added to each well, and the cells were incubated at 37 °C for another 2 h. Absorbance at 450 nm was measured using a microplate reader (Beckman).…”

“…We further showed that METTL3 plays an important role in AECII biology both in vitro and in vivo. Phosphatase and tensin homolog (PTEN) is a tumor suppressor and critical regulator of cell viability and proliferation that counteracts the activity of the phosphoinositide-3 kinase (PI3K)/Akt pathway, owing to its lipid phosphatase viability 10 . PTEN is involved in the pathogenesis of various diseases, including cardiovascular dysfunction, cancer, and neurodevelopmental disorders 11,12,13 .…”