Evidence map›Paper›PMID 29303510›Full record

ArticleExperimental & molecular medicine2018

Loss of Pten synergizes with c-Met to promote hepatocellular carcinoma development via mTORC2 pathway.

Zhong Xu, Junjie Hu, Hui Cao, Maria G Pilo, Antonio Cigliano, Zixuan Shao, Meng Xu, Silvia Ribback, Frank Dombrowski, Diego F Calvisi and 1 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Experimental & molecular medicine, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.

0numbers the graph read from it
0cells of the map it votes in
37citing papers in PubMed
2.7field-weighted citation impact, top 9% 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

37 citing papers in PubMed, 50 citations in OpenAlex.

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  12. Optimization of CRISPR-Cas system for clinical cancer therapy.Bioengineering & translational medicine · 2023
    Review
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  20. Transformation of SOX9Scientific reports · 2021
    Article
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

11 authors at 5 institutions in 3 countries.

Zhong XuDepartment of Gastroenterology, Guizhou Provincial People's Hospital, The Affiliated People's Hospital of Guizhou Medical University, Guiyang, PR China.
Junjie HuDepartment of Bioengineering and Therapeutic Sciences and Liver Center, University of California, San Francisco, CA, USA.
Hui CaoDepartment of Bioengineering and Therapeutic Sciences and Liver Center, University of California, San Francisco, CA, USA.
Maria G PiloInstitute of Pathology, University of Greifswald, Greifswald, Germany.
Antonio CiglianoInstitute of Pathology, University of Greifswald, Greifswald, Germany.
Zixuan ShaoDepartment of Bioengineering and Therapeutic Sciences and Liver Center, University of California, San Francisco, CA, USA.
Meng XuDepartment of Bioengineering and Therapeutic Sciences and Liver Center, University of California, San Francisco, CA, USA.
Silvia RibbackInstitute of Pathology, University of Greifswald, Greifswald, Germany.
Frank DombrowskiInstitute of Pathology, University of Greifswald, Greifswald, Germany.
Diego F CalvisiInstitute of Pathology, University of Greifswald, Greifswald, Germany.
Xin ChenDepartment of Bioengineering and Therapeutic Sciences and Liver Center, University of California, San Francisco, CA, USA.
Universität Greifswald · DEHubei University of Chinese Medicine · CNUniversity of California, San Francisco · USGuizhou Provincial People's Hospital · CNSan Francisco University High School · US

Funding

UCSF Liver Core CenterP30DK026743 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Jennifer Y. Chen · 1986 to 2026
$30.7M
Molecular Genetics of Liver CancersR01CA136606 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI CHEN, XIN · 2009 to 2016
$2.6M
NCI NIH HHS R01 CA136606NIDDK NIH HHS P30 DK026743
6 · The paper itself

Abstract

Hepatocellular carcinoma (HCC) is a deadly malignancy with limited treatment options. Activation of the AKT/mTOR cascade is one of the most frequent events along hepatocarcinogenesis. mTOR is a serine/threonine kinase and presents in two distinct complexes: mTORC1 and mTORC2. While mTORC1 has been extensively studied in HCC, the functional contribution of mTORC2 during hepatocarcinogenesis has not been well characterized, especially in vivo. Pten expression is one of the major mechanisms leading to the aberrant activation of the AKT/mTOR signaling. Here, we show that concomitant downregulation of Pten and upregulation of c-Met occurs in a subset of human HCC, mainly characterized by poor prognosis. Using CRISPR-based gene editing in combination with hydrodynamic injection, Pten was deleted in a subset of mouse hepatocytes (sgPten). We found that loss of Pten synergizes with overexpression of c-Met to promote HCC development in mice (sgPten/c-Met). At the molecular level, sgPten/c-Met liver tumor tissues display increased AKT and mTOR signaling. Using Rictor conditional knockout mice, we demonstrate that sgPten/c-Met-driven HCC development strictly depends on an intact mTORC2 complex. Our findings therefore support the critical role of mTORC2 in hepatocarcinogenesis. sgPten/c-Met mouse model represents a novel valuable system that can be used for the development of targeted therapy against this deadly malignancy.

Indexed as

AgedAnimalsCarcinoma, HepatocellularClustered Regularly Interspaced Short Palindromic RepeatsFemaleGene Expression Regulation, NeoplasticHumansLiver NeoplasmsMaleMechanistic Target of Rapamycin Complex 2Mice, KnockoutMiddle AgedProto-Oncogene Proteins c-metPTEN PhosphohydrolaseRapamycin-Insensitive Companion of mTOR ProteinMechanistic Target of Rapamycin Complex 2Proto-Oncogene Proteins c-metPTEN PhosphohydrolasePTEN protein, humanRapamycin-Insensitive Companion of mTOR Proteinrictor protein, mouse

Identifiers

PMID29303510
PMCPMC5992985
OpenAlexW2782207466

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.