Evidence map›Paper›PMID 38097550›Full record

ArticleCell death & disease2023

The E3 ubiquitin ligase NEDD4 regulates chemoresistance to 5-fluorouracil in colorectal cancer cells by altering JNK signalling.

Sushma Anand, Christina Nedeva, Sai V Chitti, Pamali Fonseka, Taeyoung Kang, Lahiru Gangoda, Nishat I Tabassum, Suad Abdirahman, Thiruma V Arumugam, Tracy L Putoczki and 2 more

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

Article in Cell death & disease, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
1.5field-weighted citation impact, top 17% 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

7 citing papers in PubMed, 10 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

12 authors at 3 institutions in 1 country.

Sushma Anand *Department of Biochemistry, La Trobe Institute for Molecular Science, La Trobe University, Melbourne, VIC, 3086, Australia.ORCID 0000-0003-0848-6618
Christina Nedeva *Department of Biochemistry, La Trobe Institute for Molecular Science, La Trobe University, Melbourne, VIC, 3086, Australia.
Sai V ChittiDepartment of Biochemistry, La Trobe Institute for Molecular Science, La Trobe University, Melbourne, VIC, 3086, Australia.
Pamali FonsekaDepartment of Biochemistry, La Trobe Institute for Molecular Science, La Trobe University, Melbourne, VIC, 3086, Australia.
Taeyoung KangDepartment of Biochemistry, La Trobe Institute for Molecular Science, La Trobe University, Melbourne, VIC, 3086, Australia.
Lahiru GangodaDepartment of Biochemistry, La Trobe Institute for Molecular Science, La Trobe University, Melbourne, VIC, 3086, Australia.
Nishat I TabassumDepartment of Microbiology, Anatomy, Physiology and Pharmacology, School of Agriculture, Biomedicine and Environment, Centre for Cardiovascular Biology and Disease Research, La Trobe University, Melbourne, Australia.
Suad AbdirahmanThe Walter and Eliza Hall Institute of Medical Research, Melbourne, VIC, 3052, Australia.
Thiruma V ArumugamDepartment of Microbiology, Anatomy, Physiology and Pharmacology, School of Agriculture, Biomedicine and Environment, Centre for Cardiovascular Biology and Disease Research, La Trobe University, Melbourne, Australia.ORCID 0000-0002-3377-0939
Tracy L PutoczkiThe Walter and Eliza Hall Institute of Medical Research, Melbourne, VIC, 3052, Australia.
Sharad KumarCentre for Cancer Biology, University of South Australia, Adelaide, SA, 5001, Australia.ORCID 0000-0001-7126-9814
Suresh MathivananDepartment of Biochemistry, La Trobe Institute for Molecular Science, La Trobe University, Melbourne, VIC, 3086, Australia. S.Mathivanan@latrobe.edu.au.ORCID 0000-0002-7290-5795
La Trobe University · AUThe University of Melbourne · AUUniversity of South Australia · AU

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Colorectal cancer (CRC) is the second leading cause of cancer deaths. Though chemotherapy is the main treatment option for advanced CRC, patients invariably acquire resistance to chemotherapeutic drugs and fail to respond to the therapy. Although understanding the mechanisms regulating chemoresistance has been a focus of intense research to manage this challenge, the pathways governing resistance to drugs are poorly understood. In this study, we provide evidence for the role of ubiquitin ligase NEDD4 in resistance developed against the most commonly used CRC chemotherapeutic drug 5-fluorouracil (5-FU). A marked reduction in NEDD4 protein abundance was observed in a panel of CRC cell lines and patient-derived xenograft samples that were resistant to 5-FU. Knockout of NEDD4 in CRC cells protected them from 5-FU-mediated apoptosis but not oxaliplatin or irinotecan. Furthermore, NEDD4 depletion in CRC cells reduced proliferation, colony-forming abilities and tumour growth in mice. Follow-up biochemical analysis highlighted the inhibition of the JNK signalling pathway in NEDD4-deficient cells. Treatment with the JNK activator hesperidin in NEDD4 knockout cells sensitised the CRC cells against 5-FU. Overall, we show that NEDD4 regulates cell proliferation, colony formation, tumour growth and 5-FU chemoresistance in CRC cells.

Indexed as

Colorectal NeoplasmsFluorouracilAnimalsCell Line, TumorCell ProliferationDrug Resistance, NeoplasmHumansMiceMice, KnockoutUbiquitin-Protein LigasesFluorouracilUbiquitin-Protein Ligases

Identifiers

PMID38097550
PMCPMC10721789
OpenAlexW4389740263

What OpenQuestion holds

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LicenceCC BY
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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.