Evidence map›Paper›PMID 41056281›Full record

ArticlePloS one2025

Frizzled 7 drives amplification of cancer stem-cell subpopulations and the aggressiveness and poor differentiation of human hepatocellular carcinoma.

Anaïs Lopez, Alexia Paturel, Nadim Fares, Floriane Pez, Guanxiong Wang, Patricia Gifu, Lydie Lefrançois, Jihed Chouaref, Pierre Saintigny, Janick Selves and 4 more

Abstract read
In one paragraph

Article in PloS one, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Dysregulated mScience advances · 2026
    Article
  2. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

14 authors.

Anaïs LopezINSERM U1052, CNRS-5286, Univ Lyon, Université Claude Bernard Lyon-1, Centre Léon Bérard, Centre de Recherche en Cancérologie de Lyon, Lyon, France.
Alexia PaturelINSERM U1052, CNRS-5286, Univ Lyon, Université Claude Bernard Lyon-1, Centre Léon Bérard, Centre de Recherche en Cancérologie de Lyon, Lyon, France.ORCID https://orcid.org/0000-0001-9288-9131
Nadim FaresINSERM U1052, CNRS-5286, Univ Lyon, Université Claude Bernard Lyon-1, Centre Léon Bérard, Centre de Recherche en Cancérologie de Lyon, Lyon, France.
Floriane PezINSERM U1052, CNRS-5286, Univ Lyon, Université Claude Bernard Lyon-1, Centre Léon Bérard, Centre de Recherche en Cancérologie de Lyon, Lyon, France.
Guanxiong WangINSERM U1052, CNRS-5286, Univ Lyon, Université Claude Bernard Lyon-1, Centre Léon Bérard, Centre de Recherche en Cancérologie de Lyon, Lyon, France.
Patricia GifuINSERM U1052, CNRS-5286, Univ Lyon, Université Claude Bernard Lyon-1, Centre Léon Bérard, Centre de Recherche en Cancérologie de Lyon, Lyon, France.
Lydie LefrançoisINSERM U1052, CNRS-5286, Univ Lyon, Université Claude Bernard Lyon-1, Centre Léon Bérard, Centre de Recherche en Cancérologie de Lyon, Lyon, France.
Jihed ChouarefINSERM U1052, CNRS-5286, Univ Lyon, Université Claude Bernard Lyon-1, Centre Léon Bérard, Centre de Recherche en Cancérologie de Lyon, Lyon, France.
Pierre SaintignyINSERM U1052, CNRS-5286, Univ Lyon, Université Claude Bernard Lyon-1, Centre Léon Bérard, Centre de Recherche en Cancérologie de Lyon, Lyon, France.
Janick SelvesDépartement d'Anatomie et Cytologie Pathologique, Institut Universitaire du Cancer, Toulouse Oncopôle, Toulouse, France.
Jean-Marie PeronService d'Hépato-Gastroentérologie, Hôpital Purpan, Toulouse, France.
Michel RivoireDépartement de Chirurgie et Institut de Chirurgie Expérimentale, Centre Léon Bérard, Lyon, France.
Philippe MerleINSERM U1052, CNRS-5286, Univ Lyon, Université Claude Bernard Lyon-1, Centre Léon Bérard, Centre de Recherche en Cancérologie de Lyon, Lyon, France.
Claude Caron de FromentelINSERM U1052, CNRS-5286, Univ Lyon, Université Claude Bernard Lyon-1, Centre Léon Bérard, Centre de Recherche en Cancérologie de Lyon, Lyon, France.ORCID https://orcid.org/0000-0001-7566-3958

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

FZD7 is one of the key players in the subset of WNT-TGFβ-activated hepatocellular carcinomas (HCC), but the consequences of its abnormal expression on hepatocarcinogenesis remain to be better understood. Herein, we aimed to investigate the role of the FZD7-mediated signaling in immature phenotype and aggressiveness of HCC. Firstly, 499 human HCCs were used for clinical and molecular comparisons regarding the expression of FZD7 and stemness-associated markers. We showed that FZD7 overexpression was associated with poor differentiation and, in combination with CD133, predicted a poor outcome of patients with aggressive recurrence. Next, the impact of WNT3/FZD7 signaling on the differentiation of hepatic cells was assessed in HCC cell lines, as well in the non-transformed progenitor HepaRG cell line and in primary human hepatocytes, transduced with WNT3 and FZD7-expressing lentiviruses. We demonstrated that the ectopic expression of WNT3 and FZD7 inhibited the differentiation behavior of HepaRG cells and human primary hepatocytes, amplified the pool of EpCAM(+), CD90(+) and CD133(+) subsets of HCC cell lines, and increased their cancer stem cell features. Moreover, we found that WNT3/FZD7-mediated stemness properties of cancer cells were independent of the stemness-associated marker NANOG. In conclusion, we identified the FZD7(+)/CD133(+) signature as a potential prognosis marker and molecular therapeutic target, and we strengthened the hypothesis for the involvement of FZD7 in the enrichment of a cancer stem cell pool in HCC.

Indexed as

Carcinoma, HepatocellularCell DifferentiationFrizzled ReceptorsLiver NeoplasmsNeoplastic Stem CellsAC133 AntigenAntigens, CDCell Line, TumorFemaleGene Expression Regulation, NeoplasticHepatocytesHumansMaleMiddle AgedWnt3 ProteinAC133 AntigenAntigens, CDFrizzled ReceptorsFZD7 protein, humanPROM1 protein, humanWnt3 ProteinWNT3 protein, human

Identifiers

PMID41056281
PMCPMC12503320

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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 OpenQuestion graph.