Another one bites the gut: Nuclear receptor lrh-1 in intestinal regeneration and cancer

Roberta Zerlotin, Maria Arconzo, Elena Piccinin, Antonio Moschetta

Research output: Contribution to journalReview articlepeer-review

Abstract

The process of self-renewal in normal intestinal epithelium is characterized by a fine balance between proliferation, differentiation, migration, and cell death. When even one of these aspects escapes the normal control, cellular proliferation and differentiation are impaired, with con-sequent onset of tumorigenesis. In humans, colorectal cancer (CRC) is the main pathological manifestation of this derangement. Nowadays, CRC is the world’s fourth most deadly cancer with a limited survival after treatment. Several conditions can predispose to CRC development, including dietary habits and pre-existing inflammatory bowel diseases. Given their extraordinary ability to interact with DNA, it is widely known that nuclear receptors play a key role in the regulation of intestinal epithelium, orchestrating the expression of a series of genes involved in developmental and homeostatic pathways. In particular, the nuclear receptor Liver Receptor Homolog-1 (LRH-1), highly expressed in the stem cells localized in the crypts, promotes intestine cell proliferation and renewal in both direct and indirect DNA-binding manner. Furthermore, LRH-1 is extensively correlated with diverse intestinal inflammatory pathways. These evidence shed a light in the dynamic intestinal microenvironment in which increased regenerative epithelial cell turnover, mutagenic insults, and chronic DNA damages triggered by factors within an inflammatory cell-rich microenvironment act synergistically to favor cancer onset and progression.

Original languageEnglish
Article number896
Pages (from-to)1-17
Number of pages17
JournalCancers
Volume13
Issue number4
DOIs
Publication statusPublished - Feb 2 2021

Keywords

  • Colorectal cancer (CRC)
  • Inflammatory bowel disease (IBD)
  • Intestinal stem cells (ISC)
  • Intestine
  • Liver receptor homolog 1 (LRH-1)
  • Nuclear receptors (NR)

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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