Cargando…
NKX6.3 controls gastric differentiation and tumorigenesis
NKX6.3 transcription factor is known to be an important regulator in gastric mucosal epithelial differentiation. The present study aimed to investigate whether NKX6.3 acts as an essential tumor suppressor in gastric carcinogenesis. Absent or reduced protein expression and decreased DNA copy number a...
Autores principales: | , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2015
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4695069/ https://www.ncbi.nlm.nih.gov/pubmed/26314965 |
_version_ | 1782407589123850240 |
---|---|
author | Yoon, Jung Hwan Choi, Won Suk Kim, Olga Choi, Sung Sook Lee, Eun Kyung Nam, Suk Woo Lee, Jung Young Park, Won Sang |
author_facet | Yoon, Jung Hwan Choi, Won Suk Kim, Olga Choi, Sung Sook Lee, Eun Kyung Nam, Suk Woo Lee, Jung Young Park, Won Sang |
author_sort | Yoon, Jung Hwan |
collection | PubMed |
description | NKX6.3 transcription factor is known to be an important regulator in gastric mucosal epithelial differentiation. The present study aimed to investigate whether NKX6.3 acts as an essential tumor suppressor in gastric carcinogenesis. Absent or reduced protein expression and decreased DNA copy number and mRNA transcript of the NKX6.3 gene were frequently observed in gastric cancers. Overexpression of NKX6.3 in AGS(NKX6.3) and MKN1(NKX6.3) cells markedly arrested cell proliferation by inhibiting cell cycle progression and induced apoptosis through both death receptor- and mitochondrial-pathways. In addition, stable NKX6.3 transfectants increased the expression of gastric differentiation markers, including SOX2 and Muc5ac, and decreased the expression of intestinal differentiation markers, CDX2 and Muc2. In ChIP-cloning and sequencing analyses, NKX6.3 coordinated a repertoire of target genes, some of which are clearly associated with cell cycle, differentiation and death. In particular, NKX6.3 transcriptional factor was found to bind specifically to the upstream sequences of GKN1, a gastric-specific tumor suppressor, and dramatically increase expression of the latter. Furthermore, there was a positive correlation between NKX6.3 and GKN1 expression in non-cancerous gastric mucosae. Thus, these data suggest that NKX6.3 may control the fate of gastric mucosal cells and function as a gastric tumor suppressor. |
format | Online Article Text |
id | pubmed-4695069 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-46950692016-01-20 NKX6.3 controls gastric differentiation and tumorigenesis Yoon, Jung Hwan Choi, Won Suk Kim, Olga Choi, Sung Sook Lee, Eun Kyung Nam, Suk Woo Lee, Jung Young Park, Won Sang Oncotarget Research Paper NKX6.3 transcription factor is known to be an important regulator in gastric mucosal epithelial differentiation. The present study aimed to investigate whether NKX6.3 acts as an essential tumor suppressor in gastric carcinogenesis. Absent or reduced protein expression and decreased DNA copy number and mRNA transcript of the NKX6.3 gene were frequently observed in gastric cancers. Overexpression of NKX6.3 in AGS(NKX6.3) and MKN1(NKX6.3) cells markedly arrested cell proliferation by inhibiting cell cycle progression and induced apoptosis through both death receptor- and mitochondrial-pathways. In addition, stable NKX6.3 transfectants increased the expression of gastric differentiation markers, including SOX2 and Muc5ac, and decreased the expression of intestinal differentiation markers, CDX2 and Muc2. In ChIP-cloning and sequencing analyses, NKX6.3 coordinated a repertoire of target genes, some of which are clearly associated with cell cycle, differentiation and death. In particular, NKX6.3 transcriptional factor was found to bind specifically to the upstream sequences of GKN1, a gastric-specific tumor suppressor, and dramatically increase expression of the latter. Furthermore, there was a positive correlation between NKX6.3 and GKN1 expression in non-cancerous gastric mucosae. Thus, these data suggest that NKX6.3 may control the fate of gastric mucosal cells and function as a gastric tumor suppressor. Impact Journals LLC 2015-07-22 /pmc/articles/PMC4695069/ /pubmed/26314965 Text en Copyright: © 2015 Yoon et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Paper Yoon, Jung Hwan Choi, Won Suk Kim, Olga Choi, Sung Sook Lee, Eun Kyung Nam, Suk Woo Lee, Jung Young Park, Won Sang NKX6.3 controls gastric differentiation and tumorigenesis |
title | NKX6.3 controls gastric differentiation and tumorigenesis |
title_full | NKX6.3 controls gastric differentiation and tumorigenesis |
title_fullStr | NKX6.3 controls gastric differentiation and tumorigenesis |
title_full_unstemmed | NKX6.3 controls gastric differentiation and tumorigenesis |
title_short | NKX6.3 controls gastric differentiation and tumorigenesis |
title_sort | nkx6.3 controls gastric differentiation and tumorigenesis |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4695069/ https://www.ncbi.nlm.nih.gov/pubmed/26314965 |
work_keys_str_mv | AT yoonjunghwan nkx63controlsgastricdifferentiationandtumorigenesis AT choiwonsuk nkx63controlsgastricdifferentiationandtumorigenesis AT kimolga nkx63controlsgastricdifferentiationandtumorigenesis AT choisungsook nkx63controlsgastricdifferentiationandtumorigenesis AT leeeunkyung nkx63controlsgastricdifferentiationandtumorigenesis AT namsukwoo nkx63controlsgastricdifferentiationandtumorigenesis AT leejungyoung nkx63controlsgastricdifferentiationandtumorigenesis AT parkwonsang nkx63controlsgastricdifferentiationandtumorigenesis |