# F. nucleatum blocks ferroptosis and drives oxaliplatin resistance in colorectal cancer models

- Published: 2026-11-13 17:43 UTC
- Section: Life & Health › Medicine
- Tags: Fusobacterium nucleatum, oxaliplatin resistance, ferroptosis, SLC7A11, TLR4/AP-1 pathway, colorectal cancer recurrence, tumor microbiome, 16S rRNA sequencing, HCT116 cells
- URL: https://realtech.media/news/rt-5e329a0c5bbbbd549beb0ba0_f_nucleatum_blocks/

**In cell cultures and animal experiments, the bacterium raised SLC7A11 expression via TLR4/AP-1; high bacterial load in tumor tissue coincided with more frequent recurrence in patients.**

![F. nucleatum blocks ferroptosis and drives oxaliplatin resistance in colorectal cancer models](https://realtech.media/media/2026/11/eb5c357efd955eab.jpg)
*Kgbo, Wikimedia Commons, CC BY-SA 4.0*

Researchers reported in Frontiers in Microbiology that Fusobacterium nucleatum, a bacterium found in colorectal tumors, reduces the effect of the chemotherapy drug oxaliplatin by suppressing ferroptosis, a form of iron-dependent cell death. The work combined 16S rRNA sequencing of patient tumor tissue, cell cultures, transcriptomics, biochemical assays and animal experiments. [1]

## Bacterial load and recurrence

Sequencing of tumor specimens from colorectal cancer patients showed enrichment of Negativicutes, Fusobacterium and Peptostreptococcales-Tissierellales in tissue from patients whose disease recurred. Fluorescence in situ hybridization and quantitative PCR confirmed extensive F. nucleatum colonization in recurrent specimens. [1]

Patients with a high intratumoral F. nucleatum load had a recurrence rate of 71.0 percent, versus 25.6 percent for those with low or undetectable levels. High bacterial abundance was associated with shorter recurrence-free survival over five years. For three-year recurrence, bacterial quantity gave an area under the curve of 0.696, higher than stage-based prediction, and multivariate Cox regression identified it as an independent prognostic factor. [1]

## Mechanism: SLC7A11 and TLR4/AP-1

In colorectal cancer cell lines, co-culture with F. nucleatum substantially weakened the cytotoxicity of oxaliplatin, and the effect was also confirmed in vivo. Oxaliplatin alone raised malondialdehyde, ferrous iron and oxidized glutathione, lowered reduced glutathione, and caused loss of mitochondrial cristae. In the presence of the bacterium these changes were reversed. [1]

RNA sequencing of infected HCT116 cells found 6,359 differentially expressed genes, 2,868 upregulated and 3,491 downregulated. The affected pathways included stress-activated MAPK cascades, toll-like receptor signaling and ferroptosis. SLC7A11 showed the largest expression change: oxaliplatin suppressed it, whereas F. nucleatum prevented the suppression and raised mRNA and protein levels in HCT116 and HT29 cells. [1]

Chromatin immunoprecipitation qPCR and dual-luciferase assays showed stronger binding of AP-1 c-Jun to the SLC7A11 promoter after infection, consistent with signaling through TLR4/AP-1. According to the authors, clinical data also link the TLR4/AP-1/SLC7A11 axis to F. nucleatum abundance in tumors and to recurrence. [1]

## Sources

1. [Frontiers in Microbiology](https://doi.org/10.3389/fmicb.2026.1968820)
2. [bioengineer.org](https://bioengineer.org/fusobacterium-nucleatum-blocks-colorectal-cancer-ferroptosis-to-drive-oxaliplatin-chemoresistance)

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Source: RealTech, realtech.media — https://realtech.media/news/rt-5e329a0c5bbbbd549beb0ba0_f_nucleatum_blocks/