Evidence map›Paper›PMID 39603380›Full record

ArticleCancer letters2025

PAF1-mediated transcriptional reprogramming confers docetaxel resistance in advanced prostate cancer.

Sakthivel Muniyan, Raghupathy Vengoji, Rama Krishna Nimmakayala, Parthasarathy Seshacharyulu, Balaji Perumalsamy, Zahraa Wajih Alsafwani, Sham S Kakar, Lynette M Smith, Nicole Shonka, Benjamin A Teply and 3 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cancer letters, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Review
  2. 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

13 authors.

Sakthivel MuniyanDepartment of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, 68198, USA. Electronic address: s.muniyan@unmc.edu.
Raghupathy VengojiDepartment of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, 68198, USA.
Rama Krishna NimmakayalaDepartment of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, 68198, USA.
Parthasarathy SeshacharyuluDepartment of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, 68198, USA.
Balaji PerumalsamyDepartment of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, 68198, USA.
Zahraa Wajih AlsafwaniDepartment of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, 68198, USA.
Sham S KakarDepartment of Physiology, University of Louisville School of Medicine, Louisville, KY, 40202, USA.
Lynette M SmithDepartment of Biostatistics, College of Public Health, University of Nebraska Medical Center, Omaha, NE, 68198, USA.
Nicole ShonkaDepartment of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, 68198, USA; Department of Internal Medicine, Division of Oncology and Hematology, University of Nebraska Medical Center, Omaha, NE, 68198, USA; Fred and Pamela Buffett Cancer Center, Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, NE, 68198, USA.
Benjamin A TeplyDepartment of Internal Medicine, Division of Oncology and Hematology, University of Nebraska Medical Center, Omaha, NE, 68198, USA; Fred and Pamela Buffett Cancer Center, Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, NE, 68198, USA.
Subodh M LeleDepartment of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE, 68198, USA.
Moorthy P PonnusamyDepartment of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, 68198, USA; Fred and Pamela Buffett Cancer Center, Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, NE, 68198, USA.
Surinder K BatraDepartment of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, 68198, USA; Fred and Pamela Buffett Cancer Center, Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, NE, 68198, USA. Electronic address: sbatra@unmc.edu.

Funding

UNMC/EPPLEY CANCER CENTER SUPPORT GRANTP30CA036727 · NCI · UNIVERSITY OF NEBRASKA MEDICAL CENTER · PI James Eudy · 1985 to 2026
$55.0M
Connectivity mapping identified novel combination therapy for glioblastomaR01CA273319 · NCI · UNIVERSITY OF NEBRASKA MEDICAL CENTER · PI BATRA, SURINDER K., SHONKA, NICOLE · 2022 to 2025
$2.2M
NCI NIH HHS P30 CA036727NCI NIH HHS R01 CA273319
6 · The paper itself

Abstract

Advanced prostate cancer (PCa) remains a significant clinical challenge, and docetaxel plays a significant role in disease management. Despite the efficacy of docetaxel as a first-line chemotherapy, resistance often develops. We developed three clinically relevant in vitro PCa cell models and transcriptomic analysis identified that the Paf1/RNA polymerase II complex component (PAF1)-associated pluripotent-transcription factor (TF), SOX2, plays a crucial role in docetaxel resistance. The cancer stem cell (CSC) transcriptional master regulator PAF1 is significantly higher in PCa cell lines, tumor tissues, and docetaxel resistant (DR) PCa cells than in age-matched control cells. To determine the molecular underlying and functional characteristics of PAF1 in resistance mechanisms, we performed coimmunoprecipitation, embryonic stem cell network proteins, in vitro tumor-initiating ability, and 3D multicellular organoid growth using PAF1 knockdown cells. Tet-inducible PAF1 depletion reduced the drug-efflux phenotype, tumor-initiating frequencies, and three-dimensional organoid growth of the docetaxel-resistant PCa cell lines. Functional studies also showed restoration of docetaxel sensitivity in a 3D tumorsphere model upon PAF1 depletion. PAF1 depletion was also associated with decreased pluripotent TFs and other CSC markers. This study provides a novel regulatory mechanism of docetaxel resistance in PCa through PAF1.

Indexed as

DocetaxelDrug Resistance, NeoplasmProstatic NeoplasmsAnimalsAntineoplastic AgentsCell Line, TumorGene Expression Regulation, NeoplasticHumansMaleNeoplastic Stem CellsNuclear ProteinsOrganoidsSOXB1 Transcription FactorsTranscription FactorsAntineoplastic AgentsDocetaxelNuclear ProteinsPAF1 protein, humanSOX2 protein, humanSOXB1 Transcription FactorsTranscription FactorsCancer stem-like cellsCRPCMulticellular organoid growthPAF1Therapy resistance

Identifiers

PMID39603380
PMCPMC11912633

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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.