Open AccessHigh Yap and Mll1 promote a persistent regenerative cell state induced by Notch signaling and loss of p53
Author(s) -
Julian Heuberger,
Johanna Grinat,
Frauke Kosel,
Lichao Liu,
Séverine Kunz,
Ramón Vidal,
Marlen Keil,
Johannes Haybaeck,
Sylvie Robine,
Daniel Louvard,
Christian Regenbrecht,
Anje Sporbert,
Sascha Sauer,
Björn von Eyß,
Michael Sigal,
Walter Birchmeier
Publication year - 2021
Publication title -
proceedings of the national academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.2019699118
Subject(s) - h3k4me3 , biology , notch signaling pathway , microbiology and biotechnology , carcinogenesis , signal transduction , stem cell , epigenetics , cell growth , histone , cancer research , ezh2 , genetics , cancer , gene expression , promoter , gene
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.
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