Evidence map›Paper›PMID 39532917›Full record

ArticleScientific reports2024

PKR associates with 4.1R to promote anchorage-independent growth of hepatocellular carcinoma and lead to poor prognosis.

Yusuke Okujima, Takao Watanabe, Takeshi Ito, Yasumichi Inoue, Yutaka Kasai, Yusuke Imai, Yoshiko Nakamura, Mitsuhito Koizumi, Osamu Yoshida, Yoshio Tokumoto and 7 more

Abstract read
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In one paragraph

Article in Scientific reports, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing 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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

17 authors.

Yusuke OkujimaDepartment of Gastroenterology and Metabology, Graduate School of Medicine, Ehime University, Shitsukawa, Toon, Ehime, 791-0295, Japan.
Takao WatanabeDepartment of Gastroenterology and Metabology, Graduate School of Medicine, Ehime University, Shitsukawa, Toon, Ehime, 791-0295, Japan. wtakao@m.ehime-u.ac.jp.
Takeshi ItoDivision of Molecular Pathology, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
Yasumichi InoueDepartment of Cell Signaling, Graduate School of Pharmaceutical Sciences, Nagoya City University, Nagoya, Aichi, Japan.
Yutaka KasaiDivision of Molecular Pathology, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
Yusuke ImaiDepartment of Gastroenterology and Metabology, Graduate School of Medicine, Ehime University, Shitsukawa, Toon, Ehime, 791-0295, Japan.
Yoshiko NakamuraDepartment of Gastroenterology and Metabology, Graduate School of Medicine, Ehime University, Shitsukawa, Toon, Ehime, 791-0295, Japan.
Mitsuhito KoizumiDepartment of Gastroenterology and Metabology, Graduate School of Medicine, Ehime University, Shitsukawa, Toon, Ehime, 791-0295, Japan.
Osamu YoshidaDepartment of Gastroenterology and Metabology, Graduate School of Medicine, Ehime University, Shitsukawa, Toon, Ehime, 791-0295, Japan.
Yoshio TokumotoDepartment of Gastroenterology and Metabology, Graduate School of Medicine, Ehime University, Shitsukawa, Toon, Ehime, 791-0295, Japan.
Masashi HirookaDepartment of Gastroenterology and Metabology, Graduate School of Medicine, Ehime University, Shitsukawa, Toon, Ehime, 791-0295, Japan.
Masanori AbeDepartment of Gastroenterology and Metabology, Graduate School of Medicine, Ehime University, Shitsukawa, Toon, Ehime, 791-0295, Japan.
Ryosuke KawakamiDepartment of Molecular Medicine for Pathogenesis, Graduate School of Medicine, Ehime University, Toon, Ehime, Japan.
Takashi SaitouDepartment of Molecular Medicine for Pathogenesis, Graduate School of Medicine, Ehime University, Toon, Ehime, Japan.
Takeshi ImamuraDepartment of Molecular Medicine for Pathogenesis, Graduate School of Medicine, Ehime University, Toon, Ehime, Japan.
Yoshinori MurakamiDivision of Molecular Pathology, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
Yoichi HiasaDepartment of Gastroenterology and Metabology, Graduate School of Medicine, Ehime University, Shitsukawa, Toon, Ehime, 791-0295, Japan.

Funding

Japan Society for the Promotion of Science JP21K08008
6 · The paper itself

Abstract

RNA-dependent protein kinase (PKR) may have a positive regulatory role in controlling tumor growth and progression in hepatocellular carcinoma (HCC). However, the downstream substrates and the molecular mechanism of PKR in the growth and progression of HCC have not been clarified. In this study, mass spectrometry analysis was performed with immunoprecipitated samples, and 4.1R was identified as a protein that binds to PKR. In transfected COS7 cells, an immunoprecipitation experiment showed that 4.1R binds to wild-type PKR, but not to a kinase-deficient mutant PKR, suggesting that PKR binds to 4.1R in a kinase activity-dependent manner. In HCC cell lines, HuH7 and HepG2, the expression level of 4.1R protein was shown to be regulated by protein expression and activation of PKR. Interestingly, high expression of 4.1R, as well as PKR, is associated with a worse prognosis in HCC. PKR increased HCC cell growth in both anchorage-dependent and anchorage-independent manners, whereas 4.1R was involved in HCC cell growth only in an anchorage-independent manner, not in an anchorage-dependent manner. The rescue experiment indicated that increased anchorage-independent growth of HCC cells by PKR might be caused by 4.1R. In conclusion, PKR associates with 4.1R and promotes anchorage-independent growth of HCC. The PKR-4.1R axis might be a new therapeutic target in HCC.

Indexed as

Carcinoma, HepatocellularCell ProliferationeIF-2 KinaseLiver NeoplasmsAnimalsCell Line, TumorChlorocebus aethiopsCOS CellsFemaleGene Expression Regulation, NeoplasticHep G2 CellsHumansMalePrognosisProtein BindingEIF2AK2 protein, humaneIF-2 KinaseCell lineeIF-2 kinaseErythrocyte membrane band 4.1 proteinLiver neoplasmsPrognosis

Identifiers

PMID39532917
PMCPMC11557841

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LicenceCC BY-NC-ND
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Registered trials

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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 OpenQuestion graph.