Evidence map›Paper›PMID 34685704›Full record

ArticleCells2021

The LEDGF/p75 Integrase Binding Domain Interactome Contributes to the Survival, Clonogenicity, and Tumorsphere Formation of Docetaxel-Resistant Prostate Cancer Cells.

Greisha L Ortiz-Hernandez, Evelyn S Sanchez-Hernandez, Pedro T Ochoa, Catherine C Elix, Hossam R Alkashgari, James R W McMullen, Ubaldo Soto, Shannalee R Martinez, Carlos J Diaz Osterman, Michael Mahler and 2 more

Open access · goldAbstract read
In one paragraph

Article in Cells, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
1.0field-weighted citation impact, top 25% 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

15 citing papers in PubMed, 17 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Article
  5. Article
  6. PSIP1 promotes gefitinib resistance in lung adenocarcinoma by inducing the expression of WASF3 and its downstream ITGB3/AKT signaling.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2025
    Article
  7. Review
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  12. Article
  13. An Overview of 10Cells · 2022
    Article
  14. Review
  15. Article
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 2 institutions in 2 countries.

Greisha L Ortiz-HernandezCenter for Health Disparities and Molecular Medicine, Department of Basic Sciences, Loma Linda University School of Medicine, Loma Linda, CA 92350, USA.
Evelyn S Sanchez-HernandezCenter for Health Disparities and Molecular Medicine, Department of Basic Sciences, Loma Linda University School of Medicine, Loma Linda, CA 92350, USA.
Pedro T OchoaCenter for Health Disparities and Molecular Medicine, Department of Basic Sciences, Loma Linda University School of Medicine, Loma Linda, CA 92350, USA.
Catherine C ElixCenter for Health Disparities and Molecular Medicine, Department of Basic Sciences, Loma Linda University School of Medicine, Loma Linda, CA 92350, USA.
Hossam R AlkashgariCenter for Health Disparities and Molecular Medicine, Department of Basic Sciences, Loma Linda University School of Medicine, Loma Linda, CA 92350, USA.
James R W McMullenCenter for Health Disparities and Molecular Medicine, Department of Basic Sciences, Loma Linda University School of Medicine, Loma Linda, CA 92350, USA.
Ubaldo SotoCenter for Health Disparities and Molecular Medicine, Department of Basic Sciences, Loma Linda University School of Medicine, Loma Linda, CA 92350, USA.
Shannalee R MartinezCenter for Health Disparities and Molecular Medicine, Department of Basic Sciences, Loma Linda University School of Medicine, Loma Linda, CA 92350, USA.
Carlos J Diaz OstermanCenter for Health Disparities and Molecular Medicine, Department of Basic Sciences, Loma Linda University School of Medicine, Loma Linda, CA 92350, USA.
Michael MahlerDepartment of Research, Werfen, San Diego, CA 92131, USA.
Sourav RoyBorder Biomedical Research Center, Department of Biological Sciences, College of Science, University of Texas at El Paso, El Paso, TX 79902, USA.ORCID 0000-0002-0359-994X
Carlos A CasianoCenter for Health Disparities and Molecular Medicine, Department of Basic Sciences, Loma Linda University School of Medicine, Loma Linda, CA 92350, USA.
Loma Linda University · USThe University of Texas at El Paso · US

Funding

UTEP Border Biomedical Research CenterU54MD007592 · NIMHD · UNIVERSITY OF TEXAS EL PASO · PI ARSHAD M. KHAN · 2019 to 2026
$35.1M
NIH-LLU Initiative for Maximizing Student DiversityR25GM060507 · NIGMS · LOMA LINDA UNIVERSITY · PI DE LEON, MARINO · 2001 to 2022
$11.3M
Research Training/Education CoreP20MD006988 · NIMHD · LOMA LINDA UNIVERSITY · PI DE LEON, MARINO · 2012 to 2016
$6.2M
Glucocorticoid signaling, taxane resistance, and prostate cancer mortality disparityR21CA226654 · NCI · LOMA LINDA UNIVERSITY · PI CASIANO, CARLOS A. · 2019 to 2020
$513k
NCI NIH HHS R21 CA226654NIGMS NIH HHS R25 GM060507NIMHD NIH HHS P20 MD006988NIMHD NIH HHS U54 MD007592
6 · The paper itself

Abstract

Patients with prostate cancer (PCa) receiving docetaxel chemotherapy invariably develop chemoresistance. The transcription co-activator lens epithelium-derived growth factor p75 (LEDGF/p75), also known as DFS70 and PSIP1, is upregulated in several human cancers, including PCa and promotes resistance to docetaxel and other drugs. The C-terminal region of LEDGF/p75 contains an integrase binding domain (IBD) that tethers nuclear proteins, including the HIV-1 integrase and transcription factors, to active chromatin to promote viral integration and transcription of cellular survival genes. Here, we investigated the contribution of the LEDGF/p75 IBD interactome to PCa chemoresistance. Quantitative immunoblotting revealed that LEDGF/p75 and its IBD-interacting partners are endogenously upregulated in docetaxel-resistant PCa cell lines compared to docetaxel-sensitive parental cells. Using specific human autoantibodies, we co-immunoprecipitated LEDGF/p75 with its endogenous IBD-interacting partners JPO2, menin, MLL, IWS1, ASK1, and PogZ, as well as transcription factors c-MYC and HRP2, in docetaxel-resistant cells, and confirmed their nuclear co-localization by confocal microscopy. Depletion of LEDGF/p75 and selected interacting partners robustly decreased the survival, clonogenicity, and tumorsphere formation capacity of docetaxel-resistant cells. These results implicate the LEDGF/p75 IBD interactome in PCa chemoresistance and could lead to novel therapeutic strategies targeting this protein complex for the treatment of docetaxel-resistant tumors.

Indexed as

Drug Resistance, NeoplasmAntibody SpecificityApoptosisAutoantibodiesBiomarkers, TumorCell LineageCell Line, TumorCell NucleusCell SurvivalClone CellsDocetaxelHumansIntercellular Signaling Peptides and ProteinsMaleNeoplastic Stem CellsProstatic NeoplasmsAutoantibodiesBiomarkers, TumorCDCA7L protein, humanDocetaxelIntercellular Signaling Peptides and Proteinslens epithelium-derived growth factorMEN1 protein, humanProto-Oncogene ProteinsRepressor Proteinsautoantibodiescell survivalchemoresistancedocetaxelIBD interactomeintegrase binding domainLEDGF/p75prostate cancer

Identifiers

PMID34685704
PMCPMC8534522
OpenAlexW3206797323

What OpenQuestion holds

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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.