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Could we learn more about cancer understanding placentology?

last modified Dec 04, 2020 11:43 AM

BAP1/ASXL complex modulation regulates Epithelial-Mesenchymal Transition during trophoblast differentiation and invasion

Vicente Perez-GarciaPablo Lopez-Jimenez, Graham J Burton, Ashley Moffett, Margherita Y Turco, Myriam Hemberger

 

Abstract

Normal function of the placenta depends on the earliest developmental stages when trophoblast cells differentiate and invade into the endometrium to establish the definitive maternal-fetal interface. Previously, we identified the ubiquitously expressed tumour suppressor gene BAP1 as a central factor of a novel molecular node controlling early mouse placentation. However, functional insights into how BAP1 regulates trophoblast biology are still missing. Using CRISPR/Cas9 knockout and overexpression technology, here we demonstrate that the downregulation of BAP1 protein is essential to trigger epithelial-mesenchymal transition during trophoblast differentiation associated with a gain of invasiveness. This function, which is conserved in mouse and humans, is dependent on the binding of BAP1 binding to Additional sex comb-like (ASXL1/2/3) proteins to form the Polycomb repressive deubiquitinase (PR-DUB) complex. Our results reveal that the physiological modulation of BAP1 determines the invasive properties of trophoblast, delineating a new role of the BAP1 PR-DUB complex in regulating early placentation.

 

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