Evidence mapPaperPMID 41808116Full record

ArticleCell communication and signaling : CCS2026

ICMT deficiency ameliorates weight loss and mortality, but not tumor formation in a mouse model of liver cancer.

Piotr Czarnota, Tomasz Gromowski, Anna Golda, Danuta Bryzek, Slawomir Lasota, Joanna Koziel, Mateusz Wilamowski, Jaroslaw Cisowski

Abstract read
In one paragraph

Article in Cell communication and signaling : CCS, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

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2 · The registry

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3 · Its place in the literature

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4 · The record

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5 · Who and what money

Authors and funding

8 authors.

Piotr Czarnota *Department of General Biochemistry, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Krakow, Poland.
Tomasz Gromowski *Department of General Biochemistry, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Krakow, Poland.
Anna GoldaDepartment of Microbiology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Krakow, Poland.
Danuta BryzekDepartment of Microbiology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Krakow, Poland.
Slawomir LasotaDepartment of Cell Biology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Krakow, Poland.
Joanna KozielDepartment of Microbiology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Krakow, Poland.
Mateusz WilamowskiDepartment of General Biochemistry, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Krakow, Poland.
Jaroslaw CisowskiDepartment of General Biochemistry, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Krakow, Poland. jaroslaw.cisowski@uj.edu.pl.

Funding

National Science Centre 2020/37/B/NZ4/02533
6 · The paper itself

Abstract

Liver cancer often arises in the setting of chronic liver disease and remains a major global health challenge with limited effective treatments. Isoprenylcysteine Carboxyl Methyltransferase (ICMT) is an enzyme that catalyzes the methylation of prenylated proteins containing a CAAX motif, such as RAS, a modification thought to be essential for their function. Given its role in oncogenic signaling, ICMT has emerged as a potential therapeutic target in cancer. Notably, ICMT is overexpressed in human hepatocellular carcinoma (HCC), and previous studies have shown that Icmt deletion impairs BrafV600E-driven transformation in murine fibroblasts. In this study, we investigated the role of ICMT in liver cancer using a genetically engineered mouse model with hepatocyte-specific expression of BrafV600E, combined with deletion of Trp53 and Icmt. We assessed the impact of Icmt loss on liver physiology, tumorigenesis, and global transcriptomic and proteomic landscapes. Expression of BrafV600E led to progressive body weight loss, reduced survival, hepatomegaly, vascular congestion, liver fibrosis, and tumor development. These phenotypic changes were associated with widespread alterations in gene and protein expression, particularly affecting pathways related to cell differentiation, coagulation, and metabolism. Strikingly, liver-specific Icmt deletion ameliorated several pathological features, including weight loss, early mortality, fibrosis, and vascular abnormalities. It also partially normalized the transcriptomic and proteomic profiles. However, Icmt deletion did not prevent hepatomegaly or tumor formation. In conclusion, while ICMT deletion mitigates several deleterious effects of BrafV600E-driven liver pathology, it does not block tumorigenesis. These findings suggest that ICMT is not a suitable therapeutic target for liver cancer prevention or treatment, but may have potential as a target to alleviate liver disease-associated symptoms.

Indexed as

CarcinogenesisLiver NeoplasmsProtein MethyltransferasesWeight LossAnimalsDisease Models, AnimalLiverMiceProto-Oncogene Proteins B-rafTumor Suppressor Protein p53Protein Methyltransferasesprotein-S-isoprenylcysteine O-methyltransferaseProto-Oncogene Proteins B-rafTumor Suppressor Protein p53Blood coagulationICMTLiver cancerMouse models

Identifiers

PMID41808116
PMCPMC13085728

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.