Evidence map›Paper›PMID 34748271›Full record

ArticleMolecular oncology2022

RASSF1A independence and early galectin-1 upregulation in PIK3CA-induced hepatocarcinogenesis: new therapeutic venues.

Alexander Scheiter, Katja Evert, Lucas Reibenspies, Antonio Cigliano, Katharina Annweiler, Karolina Müller, Laura-Maria-Giovanna Pöhmerer, Hongwei Xu, Guofei Cui, Timo Itzel and 10 more

Open access · goldAbstract read
In one paragraph

Article in Molecular oncology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
1.5field-weighted citation impact, top 18% of its field
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

12 citing papers in PubMed, 21 citations in OpenAlex.

  1. Review
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  7. Role of solute carrier transporters in ovarian cancer (Review).International journal of molecular medicine · 2025
    Review
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  9. Article
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  12. Smad3 Phospho-Isoform Signaling in Nonalcoholic Steatohepatitis.International journal of molecular sciences · 2022
    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

20 authors at 6 institutions in 3 countries.

Alexander ScheiterInstitute of Pathology, University of Regensburg, Germany.ORCID 0000-0001-6734-261X
Katja EvertInstitute of Pathology, University of Regensburg, Germany.
Lucas ReibenspiesInstitute of Pathology, University of Regensburg, Germany.
Antonio CiglianoInstitute of Pathology, University of Regensburg, Germany.
Katharina AnnweilerInstitute of Pathology, University Medicine of Greifswald, Germany.
Karolina MüllerCenter for Clinical Studies, University Hospital Regensburg, Germany.
Laura-Maria-Giovanna PöhmererInstitute of Pathology, University of Regensburg, Germany.
Hongwei XuDepartment of Liver Surgery, Center of Liver Transplantation, West China Hospital of Sichuan University, Chengdu, China.
Guofei CuiDepartment of Bioengineering and Therapeutic Sciences and Liver Center, University of California, San Francisco, CA, USA.
Timo ItzelDivision of Hepatology, Department of Medicine II, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
Silvia Materna-ReicheltDivision of Personalized Tumor Therapy, Fraunhofer Institute for Toxicology and Experimental Medicine, Regensburg, Germany.
Andrea ColuccioDivision of Personalized Tumor Therapy, Fraunhofer Institute for Toxicology and Experimental Medicine, Regensburg, Germany.
Kamran HonarnejadDivision of Personalized Tumor Therapy, Fraunhofer Institute for Toxicology and Experimental Medicine, Regensburg, Germany.
Andreas TeufelDivision of Hepatology, Department of Medicine II, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
Christoph BrochhausenInstitute of Pathology, University of Regensburg, Germany.
Frank DombrowskiInstitute of Pathology, University Medicine of Greifswald, Germany.
Xin ChenDepartment of Bioengineering and Therapeutic Sciences and Liver Center, University of California, San Francisco, CA, USA.
Matthias EvertInstitute of Pathology, University of Regensburg, Germany.
Diego F CalvisiInstitute of Pathology, University of Regensburg, Germany.
Kirsten UtpatelInstitute of Pathology, University of Regensburg, Germany.
University of Regensburg · DEFraunhofer Institute for Toxicology and Experimental Medicine · DEUniversity of California, San Francisco · USHeidelberg University · DEUniversitätsmedizin Greifswald · DEUniversity Hospital Regensburg · DE

Funding

Wellcome Trust
6 · The paper itself

Abstract

Aberrant activation of the phosphoinositide 3-kinase (PI3K)/AKT/mTOR and Ras/mitogen-activated protein kinase (MAPK) pathways is a hallmark of hepatocarcinogenesis. In a subset of hepatocellular carcinomas (HCCs), PI3K/AKT/mTOR signaling dysregulation depends on phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha (PIK3CA) mutations, while RAS/MAPK activation is partly attributed to promoter methylation of the tumor suppressor Ras association domain-containing protein 1 (RASSF1A). To evaluate a possible cocarcinogenic effect of PIK3CA activation and RASSF1A knockout, plasmids expressing oncogenic forms of PIK3CA (E545K or H1047R mutants) were delivered to the liver of RASSF1A knockout and wild-type mice by hydrodynamic tail vein injection combined with sleeping beauty-mediated somatic integration. Transfection of either PIK3CA E545K or H1047R mutants sufficed to induce HCCs in mice irrespective of RASSF1A mutational background. The related tumors displayed a lipogenic phenotype with upregulation of fatty acid synthase and stearoyl-CoA desaturase-1 (SCD1). Galectin-1, which was commonly upregulated in preneoplastic lesions and tumors, emerged as a regulator of SCD1. Co-inhibitory treatment with PIK3CA inhibitors and the galectin-1 inhibitor OTX008 resulted in synergistic cytotoxicity in human HCC cell lines, suggesting novel therapeutic venues.

Indexed as

Carcinoma, HepatocellularLiver NeoplasmsAnimalsCarcinogenesisCell Line, TumorClass I Phosphatidylinositol 3-KinasesGalectin 1HumansMiceMutationPhosphatidylinositol 3-KinasesProto-Oncogene Proteins c-aktTOR Serine-Threonine KinasesUp-RegulationClass I Phosphatidylinositol 3-KinasesGalectin 1Phosphatidylinositol 3-KinasesPIK3CA protein, humanPik3ca protein, mouseProto-Oncogene Proteins c-aktTOR Serine-Threonine Kinasesalpelisibgalectin-1hepatocellular carcinomaOTX008SCD1ZIP4

Identifiers

PMID34748271
PMCPMC8895452
OpenAlexW3212966227

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.