Evidence map›Paper›PMID 31450087›Full record

ArticleDNA repair2019

Inhibition of APE1-endonuclease activity affects cell metabolism in colon cancer cells via a p53-dependent pathway.

Marta Codrich, Marina Comelli, Matilde Clarissa Malfatti, Catia Mio, Dilara Ayyildiz, Chi Zhang, Mark R Kelley, Giovanni Terrosu, Carlo E M Pucillo, Gianluca Tell

Open access · greenAbstract read
In one paragraph

Article in DNA repair, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.

0numbers the graph read from it
0cells of the map it votes in
30citing papers in PubMed
1.6field-weighted citation impact, top 16% 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

30 citing papers in PubMed, 48 citations in OpenAlex.

  1. Expression of Active Apurinic Apyrimidinic Endodeoxyribonuclease 1 in Human Platelets.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026
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  2. Review
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  10. The APE1/REF-1 and the hallmarks of cancer.Molecular biology reports · 2024
    Review
  11. The inhibitor of the redox activity of APE1/REF-1, APX2009, reduces the malignant phenotype of breast cancer cells.Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologica · 2024
    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

10 authors at 2 institutions in 2 countries.

Marta CodrichLaboratory of Molecular Biology and DNA Repair, Department of Medicine, University of Udine, Udine, 33100, Italy.
Marina ComelliLaboratory of Bioenergetics, Department of Medicine, University of Udine, Udine, 33100, Italy.
Matilde Clarissa MalfattiLaboratory of Molecular Biology and DNA Repair, Department of Medicine, University of Udine, Udine, 33100, Italy.
Catia MioInstitute of Medical Genetics, Department of Medicine, University of Udine, Udine, 33100, Italy.
Dilara AyyildizLaboratory of Molecular Biology and DNA Repair, Department of Medicine, University of Udine, Udine, 33100, Italy.
Chi ZhangDepartment of Medical and Molecular Genetics, Center for Computational Biology and Bioinformatics, Indiana University, School of Medicine, Indianapolis, IN 46202, USA.
Mark R KelleyHerman B Wells Center for Pediatric Research, Department of Pediatrics and Pharmacology & Toxicology, Indiana University, School of Medicine, Indianapolis, IN 46202, USA.
Giovanni TerrosuGeneral Surgery and Transplantation Unit, Department of Medicine, University of Udine, Udine, 33100, Italy.
Carlo E M PucilloLaboratory of Immunology, Department of Medicine, University of Udine, Udine, 33100, Italy.
Gianluca TellLaboratory of Molecular Biology and DNA Repair, Department of Medicine, University of Udine, Udine, 33100, Italy. Electronic address: gianluca.tell@uniud.it.
University of Udine · ITIndiana University – Purdue University Indianapolis · US

Funding

Novel Role of Ref-1 in Pancreatic Cancer Etiology and ProgressionR01CA167291 · NCI · INDIANA UNIVERSITY INDIANAPOLIS · PI FISHEL, MELISSA L., KELLEY, MARK R. · 2013 to 2022
$5.2M
(PQ9)Mechanistic Role of APE1 and BER in chemotherapy-induced peripheral neuropathyR01CA205166 · NCI · INDIANA UNIVERSITY INDIANAPOLIS · PI FEHRENBACHER, JILL C, KELLEY, MARK R. · 2017 to 2021
$2.7M
Hyperglycemia mediated myeloproliferative diseaseR01HL140961 · NHLBI · INDIANA UNIVERSITY INDIANAPOLIS · PI KAPUR, REUBEN · 2019 to 2022
$2.3M
(PQ12) Enhancement of DNA repair in neurons via a targeted APE1 small molecule modifier to decrease and reverse chemotherapy-induced peripheral neuropathy (CIPN)R01CA231267 · NCI · INDIANA UNIVERSITY INDIANAPOLIS · PI FEHRENBACHER, JILL C, KELLEY, MARK R. · 2018 to 2022
$2.3M
NCI NIH HHS R01 CA167291NCI NIH HHS R01 CA205166NCI NIH HHS R01 CA231267NHLBI NIH HHS R01 HL140961
6 · The paper itself

Abstract

The pathogenesis of colorectal cancer (CRC) involves different mechanisms, such as genomic and microsatellite instabilities. Recently, a contribution of the base excision repair (BER) pathway in CRC pathology has been emerged. In this context, the involvement of APE1 in the BER pathway and in the transcriptional regulation of genes implicated in tumor progression strongly correlates with chemoresistance in CRC and in more aggressive cancers. In addition, the APE1 interactome is emerging as an important player in tumor progression, as demonstrated by its interaction with Nucleophosmin (NPM1). For these reasons, APE1 is becoming a promising target in cancer therapy and a powerful prognostic and predictive factor in several cancer types. Thus, specific APE1 inhibitors have been developed targeting: i) the endonuclease activity; ii) the redox function and iii) the APE1-NPM1 interaction. Furthermore, mutated p53 is a common feature of advanced CRC. The relationship between APE1 inhibition and p53 is still completely unknown. Here, we demonstrated that the inhibition of the endonuclease activity of APE1 triggers p53-mediated effects on cell metabolism in HCT-116 colon cancer cell line. In particular, the inhibition of the endonuclease activity, but not of the redox function or of the interaction with NPM1, promotes p53 activation in parallel to sensitization of p53-expressing HCT-116 cell line to genotoxic treatment. Moreover, the endonuclease inhibitor affects mitochondrial activity in a p53-dependent manner. Finally, we demonstrated that 3D organoids derived from CRC patients are susceptible to APE1-endonuclease inhibition in a p53-status correlated manner, recapitulating data obtained with HCT-116 isogenic cell lines. These findings suggest the importance of further studies aimed at testing the possibility to target the endonuclease activity of APE1 in CRC.

Indexed as

Colonic NeoplasmsDNA-(Apurinic or Apyrimidinic Site) LyaseDNA DamageEnzyme InhibitorsGene Expression Regulation, NeoplasticHCT116 CellsHumansMethyl MethanesulfonateMitochondriaMutationNucleophosminTumor Suppressor Protein p53APEX1 protein, humanDNA-(Apurinic or Apyrimidinic Site) LyaseEnzyme InhibitorsMethyl MethanesulfonateNPM1 protein, humanNucleophosminTumor Suppressor Protein p53APE1APE1-inhibitorsBERColorectal cancerOrganoidsp53

Identifiers

PMID31450087
PMCPMC7092503
OpenAlexW2966834997

What OpenQuestion holds

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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.