Evidence map›Paper›PMID 31142270›Full record

ArticleBMC cancer2019

ERO1α is a novel endogenous marker of hypoxia in human cancer cell lines.

Norio Takei, Akihiro Yoneda, Marina Kosaka, Kaori Sakai-Sawada, Yasuaki Tamura

Open access · goldAbstract read
In one paragraph

Article in BMC cancer, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed, 1 pooled it
0.8field-weighted citation impact, top 32% 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

14 citing papers in PubMed, 1 synthesis or guideline pooled it, 30 citations in OpenAlex.

  1. Pooled it
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  3. Review
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  7. Review
  8. Article
  9. ERO1-PDI Redox Signaling in Health and Disease.Antioxidants & redox signaling · 2021
    Review
  10. Tumor mutation burden as a biomarker in resected gastric cancer via its association with immune infiltration and hypoxia.Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association · 2021
    Article
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  12. Article
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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

5 authors at 1 institution in 1 country.

Norio TakeiDepartment of Molecular Therapeutics, Center for Food and Medical Innovation, Institute for the Promotion of Business-Regional Collaboration, Hokkaido University, Kita-21 Nishi-11, Kita-ku, Sapporo, 001-0021, Japan. ntakei@fmi.hokudai.ac.jp.ORCID http://orcid.org/0000-0003-0403-8332
Akihiro YonedaDepartment of Molecular Therapeutics, Center for Food and Medical Innovation, Institute for the Promotion of Business-Regional Collaboration, Hokkaido University, Kita-21 Nishi-11, Kita-ku, Sapporo, 001-0021, Japan.
Marina KosakaDepartment of Molecular Therapeutics, Center for Food and Medical Innovation, Institute for the Promotion of Business-Regional Collaboration, Hokkaido University, Kita-21 Nishi-11, Kita-ku, Sapporo, 001-0021, Japan.
Kaori Sakai-SawadaDepartment of Molecular Therapeutics, Center for Food and Medical Innovation, Institute for the Promotion of Business-Regional Collaboration, Hokkaido University, Kita-21 Nishi-11, Kita-ku, Sapporo, 001-0021, Japan.
Yasuaki TamuraDepartment of Molecular Therapeutics, Center for Food and Medical Innovation, Institute for the Promotion of Business-Regional Collaboration, Hokkaido University, Kita-21 Nishi-11, Kita-ku, Sapporo, 001-0021, Japan.
Hokkaido University · JP

Funding

Ministry of Education, Culture, Sports, Science and Technology (MEXT) in Japan 18K07060
6 · The paper itself

Abstract

backgroundHypoxia is an important factor that contributes to tumour aggressiveness and correlates with poor prognosis and resistance to conventional therapy. Therefore, identifying hypoxic environments within tumours is extremely useful for understanding cancer biology and developing novel therapeutic strategies. Several studies have suggested that carbonic anhydrase 9 (CA9) is a reliable biomarker of hypoxia and a potential therapeutic target, while pimonidazole has been identified as an exogenous hypoxia marker. However, other studies have suggested that CA9 expression is not directly induced by hypoxia and it is not expressed in all types of tumours. Thus, in this study, we focused on endoplasmic reticulum disulphide oxidase 1α (ERO1α), a protein that localises in the endoplasmic reticulum and is involved in the formation of disulphide bonds in proteins, to determine whether it could serve as a potential tumour-hypoxia biomarker.

methodsUsing quantitative real-time polymerase chain reaction, we analysed the mRNA expression of ERO1α and CA9 in different normal and cancer cell lines. We also determined the protein expression levels of ERO1α and CA9 in these cell lines by western blotting. We then investigated the hypoxia-inducible ERO1α and CA9 expression and localisation in HCT116 and HeLa cells, which express low (CA9-low) and high (CA9-high) levels of CA9, respectively. A comparative analysis was performed using pimonidazole, an exogenous hypoxic marker, as a positive control. The expression and localisation of ERO1α and CA9 in tumour spheres during hypoxia were analysed by a tumour sphere formation assay. Finally, we used a mouse model to investigate the localisation of ERO1α and CA9 in tumour xenografts using several cell lines.

resultsWe found that ERO1α expression increased under chronic hypoxia. Our results show that ERO1α was hypoxia-induced in all the tested cancer cell lines. Furthermore, in the comparative analysis using CA9 and pimonidazole, ERO1α had a similar localisation to pimonidazole in both CA9-low and CA9-high cell lines.

conclusionERO1α can serve as a novel endogenous chronic hypoxia marker that is more reliable than CA9 and can be used as a diagnostic biomarker and therapeutic target for cancer.

Indexed as

AnimalsAntigens, NeoplasmBiomarkers, TumorCarbonic Anhydrase IXCell HypoxiaCell Line, TumorHCT116 CellsHeLa CellsHT29 CellsHumansMembrane GlycoproteinsMiceNeoplasmsNeoplasm TransplantationNitroimidazolesOxidoreductasesAntigens, NeoplasmBiomarkers, TumorCA9 protein, humanCarbonic Anhydrase IXERO1A protein, humanMembrane GlycoproteinsNitroimidazolesOxidoreductasespimonidazoleBiomarkerCA9CancerERO1αHypoxia

Identifiers

PMID31142270
PMCPMC6542132
OpenAlexW2946890704

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.