PI3Kδ activity controls 1 plasticity and discriminates between EMT and stemness based on distinct TGF signalling

[en] 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  (TGF) signalling. Thus, providing an important tool to control epithelial cell fate and represents a step forward in understanding the development of aggressive carcinoma.

Disciplines :

Biochemistry, biophysics & molecular biology

Author, co-author :

Agnetti, Jean ^✱

Vanessa Bou Malham ^✱

Christophe Desterke ^✱

Nassima Benzoubir

Juan Peng Wang

Sophie Jacques

Rahmouni, Souad ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques ; Université de Liège - ULiège > GIGA > GIGA Medical Genomics - Unit of Animal Genomics

Di Valentin, Emmanuel ; Université de Liège - ULiège > Département des sciences de la vie > Virologie - Immunologie ; Université de Liège - ULiège > GIGA > GIGA Platform Viral vectors

Tuan Zea Tan

Didier Samuel

Jean Paul Thiery

Ama Gassama-Diagne

^✱ These authors have contributed equally to this work.

Language :

English

Title :

PI3Kδ activity controls 1 plasticity and discriminates between EMT and stemness based on distinct TGF signalling

Publication date :

2022

Journal title :

Communications Biology

eISSN :

2399-3642

Publisher :

Springer

Volume :

Pages :

740

Peer reviewed :

Peer Reviewed verified by ORBi

Additional URL :

https://pmc.ncbi.nlm.nih.gov/articles/PMC9314410/

Available on ORBi :

since 27 June 2022

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