4.3 Review

The gastrointestinal microbiota in colorectal cancer cell migration and invasion

Journal

CLINICAL & EXPERIMENTAL METASTASIS
Volume 38, Issue 6, Pages 495-510

Publisher

SPRINGER
DOI: 10.1007/s10585-021-10130-x

Keywords

Colorectal cancer; Microbiota; Metastasis; Epithelial-mesenchymal transition

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Funding

  1. Molecular Life and Health Program of the University of Groningen

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Colorectal carcinoma is the third most common cancer in developed countries and the second leading cause of cancer-related mortality. Interest in the influence of intestinal microbiota on CRC has increased rapidly in recent years, with factors such as Fusobacterium nucleatum and Enterococcus faecalis contributing to disease progression by affecting cell-cell adhesion and the extracellular matrix. Understanding how bacterial factors promote CRC recurrence and metastasis is essential for improving patient survival, and further human-based models are needed to study these mechanisms.
Colorectal carcinoma is the third most common cancer in developed countries and the second leading cause of cancer-related mortality. Interest in the influence of the intestinal microbiota on CRC emerged rapidly in the past few years, and the close presence of microbiota to the tumour mass creates a unique microenvironment in CRC. The gastrointestinal microbiota secrete factors that can contribute to CRC metastasis by influencing, for example, epithelial-to-mesenchymal transition. Although the role of EMT in metastasis is well-studied, mechanisms by which gastrointestinal microbiota contribute to the progression of CRC remain poorly understood. In this review, we will explore bacterial factors that contribute to the migration and invasion of colorectal carcinoma and the mechanisms involved. Bacteria involved in the induction of metastasis in primary CRC include Fusobacterium nucleatum, Enterococcus faecalis, enterotoxigenic Bacteroides fragilis, Escherichia coli and Salmonella enterica. Examples of prominent bacterial factors secreted by these bacteria include Fusobacterium adhesin A and Bacteroides fragilis Toxin. Most of these factors induce EMT-like properties in carcinoma cells and, as such, contribute to disease progression by affecting cell-cell adhesion, breakdown of the extracellular matrix and reorganisation of the cytoskeleton. It is of utmost importance to elucidate how bacterial factors promote CRC recurrence and metastasis to increase patient survival. So far, mainly animal models have been used to demonstrate this interplay between the host and microbiota. More human-based models are needed to study the mechanisms that promote migration and invasion and mimic the progression and recurrence of CRC.

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