Another One Bites the Gut: Nuclear Receptor LRH-1 in Intestinal Regeneration and Cancer
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 consequent onset...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-02-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/13/4/896 |
| _version_ | 1797395753667133440 |
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| author | Roberta Zerlotin Maria Arconzo Elena Piccinin Antonio Moschetta |
| author_facet | Roberta Zerlotin Maria Arconzo Elena Piccinin Antonio Moschetta |
| author_sort | Roberta Zerlotin |
| collection | DOAJ |
| description | 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 consequent 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. |
| first_indexed | 2024-03-09T00:40:13Z |
| format | Article |
| id | doaj.art-1624ddd7b2ad47698ee051fb187c5b70 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-09T00:40:13Z |
| publishDate | 2021-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-1624ddd7b2ad47698ee051fb187c5b702023-12-11T17:49:44ZengMDPI AGCancers2072-66942021-02-0113489610.3390/cancers13040896Another One Bites the Gut: Nuclear Receptor LRH-1 in Intestinal Regeneration and CancerRoberta Zerlotin0Maria Arconzo1Elena Piccinin2Antonio Moschetta3Department of Interdisciplinary Medicine, University of Bari “Aldo Moro”, 70124 Bari, ItalyDepartment of Interdisciplinary Medicine, University of Bari “Aldo Moro”, 70124 Bari, ItalyDepartment of Interdisciplinary Medicine, University of Bari “Aldo Moro”, 70124 Bari, ItalyDepartment of Interdisciplinary Medicine, University of Bari “Aldo Moro”, 70124 Bari, ItalyThe 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 consequent 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.https://www.mdpi.com/2072-6694/13/4/896intestineintestinal stem cells (ISC)inflammatory bowel disease (IBD)colorectal cancer (CRC)nuclear receptors (NR)liver receptor homolog 1 (LRH-1) |
| spellingShingle | Roberta Zerlotin Maria Arconzo Elena Piccinin Antonio Moschetta Another One Bites the Gut: Nuclear Receptor LRH-1 in Intestinal Regeneration and Cancer Cancers intestine intestinal stem cells (ISC) inflammatory bowel disease (IBD) colorectal cancer (CRC) nuclear receptors (NR) liver receptor homolog 1 (LRH-1) |
| title | Another One Bites the Gut: Nuclear Receptor LRH-1 in Intestinal Regeneration and Cancer |
| title_full | Another One Bites the Gut: Nuclear Receptor LRH-1 in Intestinal Regeneration and Cancer |
| title_fullStr | Another One Bites the Gut: Nuclear Receptor LRH-1 in Intestinal Regeneration and Cancer |
| title_full_unstemmed | Another One Bites the Gut: Nuclear Receptor LRH-1 in Intestinal Regeneration and Cancer |
| title_short | Another One Bites the Gut: Nuclear Receptor LRH-1 in Intestinal Regeneration and Cancer |
| title_sort | another one bites the gut nuclear receptor lrh 1 in intestinal regeneration and cancer |
| topic | intestine intestinal stem cells (ISC) inflammatory bowel disease (IBD) colorectal cancer (CRC) nuclear receptors (NR) liver receptor homolog 1 (LRH-1) |
| url | https://www.mdpi.com/2072-6694/13/4/896 |
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