The role of enteric neurons in the development and progression of colorectal cancer

Biochim Biophys Acta Rev Cancer. 2017 Dec;1868(2):420-434. doi: 10.1016/j.bbcan.2017.08.003. Epub 2017 Aug 25.

Abstract

The enteric nervous system (ENS) is the intrinsic neural network of the gastrointestinal tract, which is essential for regulating gut functions and intestinal homeostasis. The importance of the ENS is underscored by the existence of severe gastrointestinal diseases, such as Hirschsprung's disease and intestinal pseudo-obstruction, which arise when the ENS fails to develop normally or becomes dysregulated. Moreover, it is known that enteric neurons are involved in intestinal inflammation. However, the role of the ENS in colorectal cancer (CRC) carcinogenesis remains poorly understood, even though processes like perineural invasion and neoneurogenesis are important factors in CRC. Here we summarize how enteric neurons are affected during CRC and discuss the influence of enteric neurons, either direct or indirect, on the development and/or progression of CRC. Finally, we illustrate how the ENS could be targeted as a potential anti-cancer therapy, establishing the ENS as an integral part of the tumor microenvironment.

Keywords: Colorectal cancer; Enteric nervous system; Intestinal inflammation; Neurotransmitters; Tumor microenvironment.

Publication types

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

MeSH terms

  • Animals
  • Colorectal Neoplasms / etiology*
  • Colorectal Neoplasms / pathology
  • Disease Progression
  • Enteric Nervous System / physiology*
  • Humans
  • Muscle Proteins / physiology
  • Nerve Tissue Proteins / physiology
  • Neurotransmitter Agents / physiology
  • Tumor Microenvironment

Substances

  • Muscle Proteins
  • NDRG4 protein, human
  • Nerve Tissue Proteins
  • Neurotransmitter Agents