Evidence map›Paper›PMID 30377291›Full record

ArticleCell death & disease2018

Endoplasmic reticulum resident oxidase ERO1-Lalpha promotes hepatocellular carcinoma metastasis and angiogenesis through the S1PR1/STAT3/VEGF-A pathway.

Shikun Yang, Chao Yang, Fei Yu, Wenbing Ding, Yuanchang Hu, Feng Cheng, Feng Zhang, Bugao Guan, Xuehao Wang, Ling Lu and 1 more

Abstract read
In one paragraph

Article in Cell death & disease, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
43citing papers in PubMed, 1 pooled it
–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

43 citing papers in PubMed, 1 synthesis or guideline pooled it.

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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

11 authors.

Shikun YangHepatobiliary/Liver Transplantation Center, the First Affiliated Hospital of Nanjing Medical University; Key Laboratory on Living Donor Liver Transplantation of National Health and Family Planning Commission of China, Nanjing, 210029, China.
Chao YangHepatobiliary/Liver Transplantation Center, the First Affiliated Hospital of Nanjing Medical University; Key Laboratory on Living Donor Liver Transplantation of National Health and Family Planning Commission of China, Nanjing, 210029, China.
Fei YuDepartment of General surgery, People's Hospiltal of Jinhu, Jinhu, Huan'an, China.
Wenbing DingHepatobiliary/Liver Transplantation Center, the First Affiliated Hospital of Nanjing Medical University; Key Laboratory on Living Donor Liver Transplantation of National Health and Family Planning Commission of China, Nanjing, 210029, China.
Yuanchang HuHepatobiliary/Liver Transplantation Center, the First Affiliated Hospital of Nanjing Medical University; Key Laboratory on Living Donor Liver Transplantation of National Health and Family Planning Commission of China, Nanjing, 210029, China.
Feng ChengHepatobiliary/Liver Transplantation Center, the First Affiliated Hospital of Nanjing Medical University; Key Laboratory on Living Donor Liver Transplantation of National Health and Family Planning Commission of China, Nanjing, 210029, China.
Feng ZhangHepatobiliary/Liver Transplantation Center, the First Affiliated Hospital of Nanjing Medical University; Key Laboratory on Living Donor Liver Transplantation of National Health and Family Planning Commission of China, Nanjing, 210029, China. zhangfeng1958@hotmail.com.
Bugao GuanDepartment of General surgery, People's Hospiltal of Jinhu, Jinhu, Huan'an, China.
Xuehao WangHepatobiliary/Liver Transplantation Center, the First Affiliated Hospital of Nanjing Medical University; Key Laboratory on Living Donor Liver Transplantation of National Health and Family Planning Commission of China, Nanjing, 210029, China.
Ling LuHepatobiliary/Liver Transplantation Center, the First Affiliated Hospital of Nanjing Medical University; Key Laboratory on Living Donor Liver Transplantation of National Health and Family Planning Commission of China, Nanjing, 210029, China.
Jianhua RaoHepatobiliary/Liver Transplantation Center, the First Affiliated Hospital of Nanjing Medical University; Key Laboratory on Living Donor Liver Transplantation of National Health and Family Planning Commission of China, Nanjing, 210029, China. raojh@njmu.edu.cn.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Mounting evidence demonstrates that expression of ERO1α, an endoplasmic reticulum (ER)-resident oxidase, is a poor prognosis factor in a variety of human cancers. However, the clinical relevance of ERO1α and its molecular mechanisms underlying tumor progression have not been determined for hepatocellular carcinoma (HCC). ERO1α expression levels in HCC tissues and cells were detected by quantitative real-time PCR and western blotting. ERO1α shRNAs and overexpression vector were transfected into HCC cells to downregulate or upregulate ERO1α expression. In vitro and in vivo assays were performed to investigate the function of ERO1α in invasion, metastasis, and angiogenesis of HCC. We found high ERO1α expression in HCC tissues and cells that was significantly associated with metastasis and poor clinicopathologic features of vascular invasion, advanced Edmondson Grade, and TNM stage. Loss-of-function and gain-of-function studies showed that ERO1α prompted migration, invasion, epithelial-mesenchymal transition (EMT), and angiogenesis of HCC cells both in vitro and in vivo. Further studies verified a positive correlation between ERO1α and S1PR1, upregulated in metastatic HCC tissues compared with HCC tissues without metastasis. S1PR1 knockdown markedly diminished the effects of ERO1α on HCC cell migration, invasion and vascular endothelial growth factor (VEGF) expression. Most importantly, ERO1α knockdown significantly repressed the death of HCC xenograft mouse models by reducing tumor distant metastasis, and host angiogenesis by suppressing the expression of S1PR1, p-STAT3, and VEGF-A in HCC cells. Our findings suggest that ERO1α is significantly correlated with reduced survival and poor prognosis, and promotes HCC metastasis and angiogenesis by triggering the S1PR1/STAT3/VEGF-A signaling pathway. ERO1α might be a novel candidate in HCC prognosis and therapy.

Indexed as

AgedAnimalsCarcinoma, HepatocellularCell Line, TumorCell MovementCell ProliferationEpithelial-Mesenchymal TransitionFemaleGene Expression Regulation, NeoplasticHeterograftsHumansLiver NeoplasmsLung NeoplasmsMaleMembrane GlycoproteinsMiceERO1A protein, humanMembrane GlycoproteinsOxidoreductasesRNA, Small InterferingS1PR1 protein, humanSphingosine-1-Phosphate ReceptorsSTAT3 protein, humanSTAT3 Transcription FactorVascular Endothelial Growth Factor AVEGFA protein, human

Identifiers

PMID30377291
PMCPMC6207574

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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.