1. PI3Kδ activity controls plasticity and discriminates between EMT and stemness based on distinct TGFβ signaling.
- Author
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Agnetti, Jean, Bou Malham, Vanessa, Desterke, Christophe, Benzoubir, Nassima, Peng, Juan, Jacques, Sophie, Rahmouni, Souad, Di Valentin, Emanuel, Tan, Tuan Zea, Samuel, Didier, Thiery, Jean Paul, and Gassama-Diagne, Ama
- Subjects
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TRANSFORMING growth factors , *EPITHELIAL-mesenchymal transition , *PHOSPHATIDYLINOSITOL 3-kinases , *CELL polarity , *EPITHELIAL cells , *PHOSPHOINOSITIDES - Abstract
The stem cells involved in formation of the complex human body are epithelial cells that undergo apicobasal polarization and form a hollow lumen. Epithelial plasticity manifests as epithelial to mesenchymal transition (EMT), a process by which epithelial cells switch their polarity and epithelial features to adopt a mesenchymal phenotype. The connection between the EMT program and acquisition of stemness is now supported by a substantial number of reports, although what discriminates these two processes remains largely elusive. In this study, based on 3D organoid culture of hepatocellular carcinoma (HCC)-derived cell lines and AAV8-based protein overexpression in the mouse liver, we show that activity modulation of isoform δ of phosphoinositide 3-kinase (PI3Kδ) controls differentiation and discriminates between stemness and EMT by regulating the transforming growth factor β (TGFβ) signaling. This study provides an important tool to control epithelial cell fate and represents a step forward in understanding the development of aggressive carcinoma. Overexpression of isoform δ of phosphoinositide 3-kinase (PI3Kδ) promotes stemness in hepatocellular carcinoma cell lines and mouse liver, whereas its inhibition promotes EMT, suggesting a key role for PI3Kδ in epithelial plasticity. [ABSTRACT FROM AUTHOR]
- Published
- 2022
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