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High Yap and Mll1 promote a persistent regenerative cell state induced by Notch signaling and loss of p53

1 juin 2021Proceedings of the National Academy of Sciences

DOI : 10.1073/pnas.2019699118

Auteurs

Julian Heuberger, Johanna Grinat, Frauke Kosel, Lichao Liu, Séverine Kunz, Ramon Oliveira Vidal, Marlen Keil, Johannes Haybaeck, Sylvie Robine, Daniel Louvard, Christian Regenbrecht, Anje Sporbert, Sascha Sauer, Björn von Eyss, Michael Sigal, Walter Birchmeier

Résumé

Significance

Using organoids, this study shows that Notch activity and loss of p53 induce a regenerative cell state and recapitulate tumorigenesis. Mutant organoids self-renew and grow independently of essential growth factors and exhibit elevated levels of nuclear Yap, Mll1, and H3K4 trimethylation. These factors are also elevated in human colorectal cancer (CRC) and control viability of patient-derived CRC organoids. Yap interacts with Mll1, and both promote a regenerative cell state that links regenerative processes to tumorigenesis.