Gutenberg Open Science: Deletion of Cd44 inhibits metastasis formation of liver cancer in Nf2-mutant mice

Please use this identifier to cite or link to this item: http://doi.org/10.25358/openscience-9337

Full metadata record

DC Field	Value	Language
dc.contributor.author	Gerardo-Ramírez, Monserrat	-
dc.contributor.author	Giam, Vanessa	-
dc.contributor.author	Becker, Diana	-
dc.contributor.author	Groth, Marco	-
dc.contributor.author	Hartmann, Nils	-
dc.contributor.author	Morrison, Helen	-
dc.contributor.author	May-Simera, Helen L.	-
dc.contributor.author	Radsak, Markus P.	-
dc.contributor.author	Marquardt, Jens U.	-
dc.contributor.author	Galle, Peter R.	-
dc.contributor.author	Herrlich, Peter	-
dc.contributor.author	Straub, Beate K.	-
dc.contributor.author	Hartmann, Monika	-
dc.date.accessioned	2023-08-08T07:01:58Z	-
dc.date.available	2023-08-08T07:01:58Z	-
dc.date.issued	2023	-
dc.identifier.uri	https://openscience.ub.uni-mainz.de/handle/20.500.12030/9355	-
dc.description.abstract	Primary liver cancer is the third leading cause of cancer-related death worldwide. An increasing body of evidence suggests that the Hippo tumor suppressor pathway plays a critical role in restricting cell proliferation and determining cell fate during physiological and pathological processes in the liver. Merlin (Moesin-Ezrin-Radixin-like protein) encoded by the NF2 (neurofibromatosis type 2) gene is an upstream regulator of the Hippo signaling pathway. Targeting of Merlin to the plasma membrane seems to be crucial for its major tumor-suppressive functions; this is facilitated by interactions with membrane-associated proteins, including CD44 (cluster of differentiation 44). Mutations within the CD44-binding domain of Merlin have been reported in many human cancers. This study evaluated the relative contribution of CD44- and Merlin-dependent processes to the development and progression of liver tumors. To this end, mice with a liver-specific deletion of the Nf2 gene were crossed with Cd44-knockout mice and subjected to extensive histological, biochemical and molecular analyses. In addition, cells were isolated from mutant livers and analyzed by in vitro assays. Deletion of Nf2 in the liver led to substantial liver enlargement and generation of hepatocellular carcinomas (HCCs), intrahepatic cholangiocarcinomas (iCCAs), as well as mixed hepatocellular cholangiocarcinomas. Whilst deletion of Cd44 had no influence on liver size or primary liver tumor development, it significantly inhibited metastasis formation in Nf2-mutant mice. CD44 upregulates expression of integrin β2 and promotes transendothelial migration of liver cancer cells, which may facilitate metastatic spreading. Overall, our results suggest that CD44 may be a promising target for intervening with metastatic spreading of liver cancer.	en_GB
dc.description.sponsorship	Gefördert durch die Deutsche Forschungsgemeinschaft (DFG) - Projektnummer 491381577	de
dc.language.iso	eng	de
dc.rights	CC BY	*
dc.rights.uri	https://creativecommons.org/licenses/by/4.0/	*
dc.subject.ddc	610 Medizin	de_DE
dc.subject.ddc	610 Medical sciences	en_GB
dc.title	Deletion of Cd44 inhibits metastasis formation of liver cancer in Nf2-mutant mice	en_GB
dc.type	Zeitschriftenaufsatz	de
dc.identifier.doi	http://doi.org/10.25358/openscience-9337	-
jgu.type.contenttype	Scientific article	de
jgu.type.dinitype	article	en_GB
jgu.type.version	Published version	de
jgu.type.resource	Text	de
jgu.organisation.department	FB 04 Medizin	de
jgu.organisation.number	2700	-
jgu.organisation.name	Johannes Gutenberg-Universität Mainz	-
jgu.rights.accessrights	openAccess	-
jgu.journal.title	Cells	de
jgu.journal.volume	12	de
jgu.journal.issue	9	de
jgu.pages.alternative	1257	de
jgu.publisher.year	2023	-
jgu.publisher.name	MDPI	de
jgu.publisher.place	Basel	de
jgu.publisher.issn	2073-4409	de
jgu.organisation.place	Mainz	-
jgu.subject.ddccode	610	de
jgu.publisher.doi	10.3390/cells12091257	de
jgu.organisation.ror	https://ror.org/023b0x485	-
jgu.subject.dfg	Lebenswissenschaften	de
Appears in collections:	DFG-491381577-G

Files in This Item:

	File	Description	Size	Format
	deletion_of_cd44_inhibits_met-20230802114757395.pdf		13.39 MB	Adobe PDF	View/Open

Show simple item record