Effects of Tumor-Associated E. coli Metabolites on Migration of Colorectal Cancer Cells

Ignatova, Nadezhda; Pryazhnikova, Maria; Seliverstov, Andrey; Abidullina, Alina; Gamayunov, Sergey; Shirmanova, Marina; Druzhkova, Irina

doi:10.22092/ari.2025.368270.3499

Effects of Tumor-Associated E. coli Metabolites on Migration of Colorectal Cancer Cells

Articles in Press

Document Type : Original Articles

Authors

¹ Department of Epidemiology, Microbiology and Evidence-Based Medicine, Privolzhsky Research Medical University, Nizhny Novgorod, Russia

² Institute of Experimental Oncology and Biomedical Technologies, Privolzhsky Research Medical University, Nizhny Novgorod, Russia

³ Central Research Laboratory, Privolzhsky Research Medical University, Nizhny Novgorod, Russia

⁴ Nizhny Novgorod Regional Oncologic Hospital, Nizhny Novgorod, Russia

10.22092/ari.2025.368270.3499

Abstract

Colorectal tumors have a close connection with the gut microbiome. Correlation between rearrangement in microbiome composition and disease progression has already been shown. However, the questions about the mechanisms underlying microorganisms and cancer cells interaction and the immediate effects of tumor-associated microbiomes on cancer cells remain open. In this work, we investigated the effects of metabolites of tumor-associated E.coli strains on migration of human colorectal cancer cell lines (HCT116, SW480 and HT29). We showed differenties in some biochemical enzime activity of E.coli strains and the spectrum of synthesized organic acids by tumor-associated and probiotic E.coli M-17 strains. Most of the strains associated with colorectal cancer were unable to utilize sucrose. Specifically, tumor-associated E.coli produced more fumaric, malic and maleic acids, whereas the E.coli M-17 produced more short fatty acids such as propionic, 2-oxobutyric and α-ketoglutaric acids. Upon exposure to metabolites from tumor-associated E.coli strains, HCT116 and SW480 cells showed an increased migration activity and HT29 cells - decreased migration activity in 2D and 3D culture models. Immunocytochemistry assay revealed decrease of E-cadherin in HCT116 and SW480 cells and FAK- in HT29, which explain different effects of E.coli metabolites on migratory capacity of colorectal cancer cells. Therefore, these results suggest that the effect of tumor-associated E.coli strains on cancer cells migration depends on their innate type of migration and enhance FAK-dependent single-cell migration accompanied by the loss of E-cadherin in cancer cells with initially low FAK expression. At the same time, this effect was not observed in cancer cells with collective migration phenotype.

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