Evidence map›Paper›PMID 41013770›Full record

ArticleBreast cancer research : BCR2025

An enteropathogenic microbial toxin modulates the breast cancer epigenome resulting in concurrent silencing of tumor suppressor genes.

Deepak Verma, Deeptashree Nandi, Sheetal Parida, Archisha Saxena, Dipali Sharma

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Breast cancer research : BCR, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing 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

4 citing papers in PubMed.

  1. Review
  2. Review
  3. Review
  4. Review
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

5 authors.

Deepak Verma *Department of Oncology, The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, 1650 Orleans Street, CRB 1, Rm 145, Baltimore, MD, 21231, USA.
Deeptashree Nandi *Department of Oncology, The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, 1650 Orleans Street, CRB 1, Rm 145, Baltimore, MD, 21231, USA.
Sheetal ParidaDepartment of Oncology, The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, 1650 Orleans Street, CRB 1, Rm 145, Baltimore, MD, 21231, USA.
Archisha SaxenaDepartment of Oncology, The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, 1650 Orleans Street, CRB 1, Rm 145, Baltimore, MD, 21231, USA.
Dipali SharmaDepartment of Oncology, The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, 1650 Orleans Street, CRB 1, Rm 145, Baltimore, MD, 21231, USA. dsharma7@jhmi.edu.

Funding

Breast Cancer Research Foundation 90047965Congressionally Directed Medical Research Programs BC191572Congressionally Directed Medical Research Programs,United States BC210668
6 · The paper itself

Abstract

backgroundRecent studies have determined a close association between host microbiota and breast cancer initiation, growth and therapeutic outcomes. We previously uncovered how enterotoxigenic Bacteroides fragilis (ETBF), a gut microbe present in malignant breast tissue, aids breast cancer development and metastatic progression via activating multiple oncogenic pathways and modulating breast tumor microenvironment. Brief exposure to ETBF-secreted toxin, BFT (Bacteroides fragilis toxin), imparts long-term oncogenic, pro-stemness and pro-metastasis memory in breast cancer cells indicating the involvement of epigenetic alterations hence, we aimed to investigate the potential involvement of epigenetics in biological impact of ETBF in breast cancer.

methodsRNA sequencing and Infinium methylation EPIC microarray were performed in mammary tumors developed from the BFT-exposed breast cancer cells. Alterations in the expression of tumor suppressor genes (TSGs) were assessed using RT-PCR, ICC and IHC. Demethylation agent and HDAC inhibitor were utilized to rescue the expression of BFT-mediated hypermethylated TSGs, and examine the migration/invasion potential of BFT-exposed breast cancer cells.

resultsEPIC methylation microarray analysis of BFT-exposed mammary tumors uncovered 64 differentially methylated significant CpG sites whose analysis led to the identification of 26 hypomethylated and 156 hypermethylated genes. Of the hypermethylated genes, also showing reduced expression in RNA-seq in BFT-exposed group, we identified five important TSGs, namely, NF2, RSK3, FAT4, DCN and DOK2. Survival analysis revealed that decreased expression of these TSGs associated with worse prognosis. While BFT exposure reduced the expression of these TSGs, treatment with Azacytidine or/and Trichostatin A resulted in rescue of the TSGs from BFT-induced repression while mitigating BFT-driven migration and invasion of breast cancer cells.

conclusionsCollectively, BFT exposure epigenetically modifies the expression of TSGs and impacts migration/invasion potential of breast cancer cells, and treatment with demethylation agent(s) and HDAC inhibitors effectively diminishes the functional impact of BFT.

Indexed as

Bacterial ToxinsBreast NeoplasmsEpigenomeGene SilencingGenes, Tumor SuppressorAnimalsBacteroides fragilisCell Line, TumorCell MovementDNA MethylationEpigenesis, GeneticFemaleGene Expression Regulation, NeoplasticHumansMiceTumor MicroenvironmentBacterial ToxinsB. fragilisBFTBreast cancerEpigeneticsETBFMethylationMicrobiotaTumor suppressor

Identifiers

PMID41013770
PMCPMC12465748

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
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 Socratic graph.