The DOI matches its Crossref record; 58 of the 58 references it cites were found in a registry or an index.
FGF19 and its analog Aldafermin cooperate with MYC to induce aggressive hepatocarcinogenesis
Open accessPublished version of a preprint
Abstract
FGF19 hormone has pleiotropic metabolic functions, including the modulation of insulin sensitivity, glucose/lipid metabolism and energy homeostasis. On top of its physiological metabolic role, FGF19 has been identified as a potentially targetable oncogenic driver, notably in hepatocellular carcinoma (HCC). Nevertheless, FGF19 remained an attractive candidate for treatment of metabolic disease, prompting the development of analogs uncoupling its metabolic and tumor-promoting activities. Using pre-clinical mice models of somatic mutation driven HCC, we assessed the oncogenicity of FGF19 in combination with frequent HCC tumorigenic alterations: p53 inactivation, CTNNB1 mutation, CCND1 or MYC overexpression. Our data revealed a strong oncogenic cooperation between FGF19 and MYC. Most importantly, we show that this oncogenic synergy is conserved with a FGF19-analog Aldafermin (NGM282), designed to solely mimic the hormone’s metabolic functions. In particular, even a short systemic treatment with recombinant proteins triggered rapid appearance of proliferative foci of MYC-expressing hepatocytes. The fact that FGF19 analog Aldafermin is not fully devoid of the hormone’s oncogenic properties raises concerns in the context of its potential use for patients with damaged, mutation-prone liver.
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Metadata
- Authors
- Ursic-Bedoya, J., Desandré, G., Chavey, C., Marie, P., Polizzi, A., Rivière, B., Guillou, H., Assenat, E., Hibner, U., & Gregoire, D.
- Affiliations
- Centre National de la Recherche Scientifique (FR)
- Université Toulouse III - Paul Sabatier (FR)
- Université de Montpellier (FR)
- Corresponding author
- Desandré, Guillaume
- ORCID
- Venue
- EMBO Molecular Medicine
- Published
- 2024-01-16
- Volume
- 16
- Issue
- 2
- Pages
- 238-250
- ISSN
- 1757-4676 (ISSN-L)
- 1757-4684
- PMC
- PMC10897482
- OpenAlex
- W4390904460
- Cited by
- 11
- References
- 58
- Citations by year
- 2026: 5 · 2025: 3 · 2024: 3
- FWCI
- 1.50
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- EMBO Molecular Medicine (publishedVersion, cc-by)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- HAL (submittedVersion, cc-by-nc-nd)
- HAL (submittedVersion, cc-by-nc-sa)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Association Française pour l'Etude du Foie (AAP_2021)
- SIRIC Montpellier (Cancer Grant INCa_Inserm_DGOS_12553)
- Fondation ARC pour la Recherche sur le Cancer (2019)
- Institut National Du Cancer (2019-134)
- ITMO Cancer (EVA-Plan cancer INSERM HTE-201610)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fibroblast Growth Factor Research
- Health Sciences › Medicine › Hepatology › Hepatocellular Carcinoma Treatment and Prognosis
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Keywords
- FGF19, c-Myc, hepatocellular carcinoma, hepatocarcinogenesis, oncogene cooperation, p53 inactivation, CTNNB1 mutation, hepatocyte proliferation, drug safety concerns
- MeSH terms
- Animals, Fibroblast Growth Factors, Carcinoma, Hepatocellular, Hormones, Humans, Liver Neoplasms, Mice
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