The gastrointestinal microbiota in colorectal cancer cell migration and invasion

Clin Exp Metastasis. 2021 Dec;38(6):495-510. doi: 10.1007/s10585-021-10130-x. Epub 2021 Nov 8.

Abstract

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.

Keywords: Colorectal cancer; Epithelial-mesenchymal transition; Metastasis; Microbiota.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Bacteria / metabolism*
  • Bacteria / pathogenicity
  • Bacterial Proteins / metabolism*
  • Bacterial Toxins / metabolism*
  • Carcinoma / metabolism
  • Carcinoma / microbiology*
  • Carcinoma / secondary
  • Cell Movement*
  • Colorectal Neoplasms / metabolism
  • Colorectal Neoplasms / microbiology*
  • Colorectal Neoplasms / pathology
  • Dysbiosis
  • Gastrointestinal Microbiome*
  • Host-Pathogen Interactions
  • Humans
  • Neoplasm Invasiveness
  • Signal Transduction

Substances

  • Bacterial Proteins
  • Bacterial Toxins