Tumor-Infiltrating Bacteria Disrupt Cancer Epithelial Cell Interactions and Induce Cell-Cycle Arrest

Authors

Jorge Luis Galeano Niño
Falk Ponath
Victor A Ajisafe
Clara R Becker
Andrew G Kempchinsky
Martha A Zepeda-Rivera
Javier A Gomez
Hanrui Wu
Jessica G Terrazas
Heather Bouzek
Elizabeth Cromwell
Pritha Chanana
Matthew Wong
Ashish Damania
Michael G White
Y Nancy You
Scott Kopetz
Nadim J Ajami
Jennifer A Wargo
Christopher D Johnston
Susan Bullman

Language

English

Publication Date

1-12-2026

Journal

Cancer Cell

DOI

10.1016/j.ccell.2025.09.010

PMID

41106380

PMCID

PMC12774452

PubMedCentral® Posted Date

1-7-2026

PubMedCentral® Full Text Version

Author MSS

Abstract

Tumor-infiltrating bacteria are increasingly recognized as modulators of cancer progression and therapy resistance. We describe a mechanism by which extracellular intratumoral bacteria, including Fusobacterium, modulate cancer epithelial cell behavior. Spatial imaging and single-cell spatial transcriptomics show that these bacteria predominantly localize extracellularly within tumor microniches of colorectal and oral cancers, characterized by reduced cell density, transcriptional activity, and proliferation. In vitro, Fusobacterium nucleatum disrupts epithelial contacts, inducing G0-G1 arrest and transcriptional quiescence. This state confers 5-fluorouracil resistance and remodels the tumor microenvironment. Findings were validated by live-cell imaging, spatial profiling, mouse models, and a 52-patient colorectal cancer cohort. Transcriptomics reveals downregulation of cell cycle, transcription, and antigen presentation genes in bacteria-enriched regions, consistent with a quiescent, immune-evasive phenotype. In an independent rectal cancer cohort, high Fusobacterium burden correlates with reduced therapy response. These results link extracellular bacteria to cancer cell quiescence and chemoresistance, highlighting microbial-tumor interactions as therapeutic targets.

Keywords

Humans, Animals, Fusobacterium nucleatum, Mice, Epithelial Cells, Tumor Microenvironment, Colorectal Neoplasms, Cell Cycle Checkpoints, Fluorouracil, Drug Resistance, Neoplasm, Cell Line, Tumor, Cell Communication, Female

Published Open-Access

yes

Recommended Citation

Galeano Niño, Jorge Luis; Ponath, Falk; Ajisafe, Victor A; et al., "Tumor-Infiltrating Bacteria Disrupt Cancer Epithelial Cell Interactions and Induce Cell-Cycle Arrest" (2026). Faculty, Staff and Student Publications. 5391.
https://digitalcommons.library.tmc.edu/uthgsbs_docs/5391