Evidence map›Paper›PMID 31968140›Full record

ArticleCancer science2020

Modulation of Nqo1 activity intercepts anoikis resistance and reduces metastatic potential of hepatocellular carcinoma.

Masahiro Shimokawa, Tomoharu Yoshizumi, Shinji Itoh, Norifumi Iseda, Kazuhito Sakata, Kyohei Yugawa, Takeo Toshima, Noboru Harada, Toru Ikegami, Masaki Mori

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

Article in Cancer science, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.

0numbers the graph read from it
0cells of the map it votes in
34citing papers in PubMed
2.3field-weighted citation impact, top 11% 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

34 citing papers in PubMed, 50 citations in OpenAlex.

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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

10 authors at 1 institution in 1 country.

Masahiro ShimokawaDepartment of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Tomoharu YoshizumiDepartment of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Shinji ItohDepartment of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.ORCID https://orcid.org/0000-0003-0382-2520
Norifumi IsedaDepartment of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Kazuhito SakataDepartment of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Kyohei YugawaDepartment of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.ORCID https://orcid.org/0000-0001-5121-682X
Takeo ToshimaDepartment of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Noboru HaradaDepartment of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Toru IkegamiDepartment of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Masaki MoriDepartment of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Kyushu University · JP

Funding

Japan Society for the Promotion of Science JP-16K10576 and 19K09198
6 · The paper itself

Abstract

The processing of intracellular reactive oxygen species (ROS) by nuclear factor erythroid-derived 2-like 2 (Nrf2) and NADPH quinone oxidoreductase 1 (Nqo1) is important for tumor metastasis. However, the clinical and biological significance of Nrf2/Nqo1 expression in hepatocellular carcinoma (HCC) remains unclear. We aimed to clarify the clinical importance of Nrf2/Nqo1 expression in HCC and evaluate the association of Nrf2/Nqo1 expression with HCC metastasis. We also evaluated the impact of Nqo1 modulation on HCC metastatic potential. We used spheroids derived from HCC cell lines. In anchorage-independent culture, HCC cells showed increased ROS, leading to the upregulation of Nrf2/Nqo1. Futile stimulation of Nqo1 by β-lapachone induces excessive oxidative stress and dramatically increased anoikis sensitivity, finally diminishing the spheroid formation ability, which was far stronger than depletion of Nqo1. We analyzed 117 cases of primary HCC who underwent curative resection. Overexpression of Nrf2/Nqo1 in primary HCC was associated with tumor size, high α-fetoprotein, and des-γ-carboxy-prothrombin levels. Overexpression of Nrf2/Nqo1 was also associated with multiple intrahepatic recurrences (P = .0073) and was an independent risk factor for poor prognosis (P = .0031). NADPH quinone oxidoreductase 1 plays an important role in anchorage-independent survival, which is essential for survival for circulation and distant metastasis of HCC cells. These results suggest that targeting Nqo1 activity could be a potential strategy for HCC adjuvant therapy.

Indexed as

AgedAnoikisApoptosisCarcinoma, HepatocellularCell Line, TumorCell ProliferationFemaleGene Expression Regulation, NeoplasticHumansLiver NeoplasmsMaleMiddle AgedNAD(P)H Dehydrogenase (Quinone)NaphthoquinonesNeoplasm MetastasisNeoplasm Recurrence, Localbeta-lapachoneNAD(P)H Dehydrogenase (Quinone)NaphthoquinonesNFE2L2 protein, humanNF-E2-Related Factor 2NQO1 protein, humanReactive Oxygen Specieshepatocellular carcinomametastasisNqo1Nrf2oxidative stress

Identifiers

PMID31968140
PMCPMC7156873
OpenAlexW3001759208

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
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.