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@ARTICLE{Seehawer:137637,
author = {M. Seehawer and F. Heinzmann and L. D'Artista and J. Harbig
and P.-F. Roux and L. Hoenicke and H. Dang and S. Klotz and
L. Robinson and G. Doré and N. Rozenblum and T.-W. Kang and
R. Chawla and T. Buch and M. Vucur and M. Roth and J. Zuber
and T. Luedde and B. Sipos and T. Longerich and M.
Heikenwälder$^*$ and X. W. Wang and O. Bischof and L.
Zender$^*$},
title = {{N}ecroptosis microenvironment directs lineage commitment
in liver cancer.},
journal = {Nature},
volume = {562},
number = {7725},
issn = {1476-4687},
address = {London [u.a.]},
publisher = {Nature Publ. Group},
reportid = {DKFZ-2018-01517},
pages = {69-75},
year = {2018},
abstract = {Primary liver cancer represents a major health problem. It
comprises hepatocellular carcinoma (HCC) and intrahepatic
cholangiocarcinoma (ICC), which differ markedly with regards
to their morphology, metastatic potential and responses to
therapy. However, the regulatory molecules and tissue
context that commit transformed hepatic cells towards HCC or
ICC are largely unknown. Here we show that the hepatic
microenvironment epigenetically shapes lineage commitment in
mosaic mouse models of liver tumorigenesis. Whereas a
necroptosis-associated hepatic cytokine microenvironment
determines ICC outgrowth from oncogenically transformed
hepatocytes, hepatocytes containing identical oncogenic
drivers give rise to HCC if they are surrounded by apoptotic
hepatocytes. Epigenome and transcriptome profiling of mouse
HCC and ICC singled out Tbx3 and Prdm5 as major
microenvironment-dependent and epigenetically regulated
lineage-commitment factors, a function that is conserved in
humans. Together, our results provide insight into lineage
commitment in liver tumorigenesis, and explain molecularly
why common liver-damaging risk factors can lead to either
HCC or ICC.},
cin = {F180 / V076 / L801},
ddc = {500},
cid = {I:(DE-He78)F180-20160331 / I:(DE-He78)V076-20160331 /
I:(DE-He78)L801-20160331},
pnm = {316 - Infections and cancer (POF3-316)},
pid = {G:(DE-HGF)POF3-316},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:30209397},
doi = {10.1038/s41586-018-0519-y},
url = {https://inrepo02.dkfz.de/record/137637},
}