Evidence map›Paper›PMID 33446568›Full record

ArticleGenes & development2021

ATDC binds to KEAP1 to drive NRF2-mediated tumorigenesis and chemoresistance in pancreatic cancer.

Vinee Purohit, Lidong Wang, Huibin Yang, Jiufeng Li, Gina M Ney, Erica R Gumkowski, Akash J Vaidya, Annie Wang, Amit Bhardwaj, Ende Zhao and 9 more

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

Article in Genes & development, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
–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

18 citing papers in PubMed, 36 citations in OpenAlex.

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  14. Identification of a Novel Oncogenic Fusion GeneInternational journal of molecular sciences · 2022
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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

19 authors at 2 institutions in 1 country.

Vinee Purohit *Perlmutter Cancer Center, New York University, New York, New York 10016, USA.
Lidong Wang *Perlmutter Cancer Center, New York University, New York, New York 10016, USA.
Huibin YangDepartment of Radiation Oncology, University of Michigan Health System, Ann Arbor, Michigan 48109, USA.
Jiufeng LiPerlmutter Cancer Center, New York University, New York, New York 10016, USA.
Gina M NeyDepartment of Pediatric Oncology, University of Michigan Health System, Ann Arbor, Michigan 48109, USA.
Erica R GumkowskiDepartment of Molecular and Integrative Physiology, University of Michigan Health System, Ann Arbor, Michigan 48109, USA.
Akash J VaidyaDepartment of Molecular and Integrative Physiology, University of Michigan Health System, Ann Arbor, Michigan 48109, USA.
Annie WangPerlmutter Cancer Center, New York University, New York, New York 10016, USA.
Amit BhardwajPerlmutter Cancer Center, New York University, New York, New York 10016, USA.
Ende ZhaoPerlmutter Cancer Center, New York University, New York, New York 10016, USA.
Igor DolgalevPerlmutter Cancer Center, New York University, New York, New York 10016, USA.
Andrea ZamperonePerlmutter Cancer Center, New York University, New York, New York 10016, USA.
Ethan V AbelDepartment of Molecular and Integrative Physiology, University of Michigan Health System, Ann Arbor, Michigan 48109, USA.
Marina Pasca Di MaglianoDepartment of Surgery, University of Michigan Health System, Ann Arbor, Michigan 48109, USA.ORCID 0000-0001-9632-9035
Howard C CrawfordDepartment of Molecular and Integrative Physiology, University of Michigan Health System, Ann Arbor, Michigan 48109, USA.
Daniel DiolaitiPerlmutter Cancer Center, New York University, New York, New York 10016, USA.
Thales Y PapagiannakopoulosPerlmutter Cancer Center, New York University, New York, New York 10016, USA.
Costas A LyssiotisDepartment of Molecular and Integrative Physiology, University of Michigan Health System, Ann Arbor, Michigan 48109, USA.ORCID 0000-0001-9309-6141
Diane M SimeonePerlmutter Cancer Center, New York University, New York, New York 10016, USA.
New York University · USUniversity of Michigan · US

Funding

Early Detection Biomarkers in Pancreatic AdenocarcinomaR01CA131045 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI SIMEONE, DIANE M · 2008 to 2019
$3.2M
Metaplastic Tuft Cells in Pancreatic CancerR01CA247516 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI CRAWFORD, HOWARD C. · 2020 to 2024
$2.3M
Oncogenic Function of ATDC in Bladder CancerR01CA174836 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI SIMEONE, DIANE M · 2014 to 2018
$2.3M
Stromal metabolism promotes therapeutic resistance in pancreatic cancerR01CA248160 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI LYSSIOTIS, COSTAS ANDREAS · 2020 to 2024
$2.0M
Targeting metabolic stress to induce pancreatic tumor cell deathR01CA244931 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI LYSSIOTIS, COSTAS ANDREAS · 2020 to 2024
$1.9M
NCI NIH HHS R01 CA131045NCI NIH HHS R01 CA174836NCI NIH HHS R01 CA244931NCI NIH HHS R01 CA247516NCI NIH HHS R01 CA248160
6 · The paper itself

Abstract

Pancreatic ductal adenocarcinoma is a lethal disease characterized by late diagnosis, propensity for early metastasis and resistance to chemotherapy. Little is known about the mechanisms that drive innate therapeutic resistance in pancreatic cancer. The ataxia-telangiectasia group D-associated gene (ATDC) is overexpressed in pancreatic cancer and promotes tumor growth and metastasis. Our study reveals that increased ATDC levels protect cancer cells from reactive oxygen species (ROS) via stabilization of nuclear factor erythroid 2-related factor 2 (NRF2). Mechanistically, ATDC binds to Kelch-like ECH-associated protein 1 (KEAP1), the principal regulator of NRF2 degradation, and thereby prevents degradation of NRF2 resulting in activation of a NRF2-dependent transcriptional program, reduced intracellular ROS and enhanced chemoresistance. Our findings define a novel role of ATDC in regulating redox balance and chemotherapeutic resistance by modulating NRF2 activity.

Indexed as

CarcinogenesisDNA-Binding ProteinsDrug Resistance, NeoplasmHumansKelch-Like ECH-Associated Protein 1NF-E2-Related Factor 2Pancreatic NeoplasmsProtein BindingTranscription FactorsDNA-Binding ProteinsKEAP1 protein, humanKelch-Like ECH-Associated Protein 1NFE2L2 protein, humanNF-E2-Related Factor 2Transcription FactorsTRIM29 protein, humanATDC (Trim29)chemotherapeutic resistancepancreatic cancertumor growth and invasion

Identifiers

PMID33446568
PMCPMC7849366
OpenAlexW3125576433

What OpenQuestion holds

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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.