NKX6.3 controls gastric differentiation and tumorigenesis

Oncotarget
Jung Hwan YoonWon Sang Park

Abstract

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 AGSNKX6.3 and MKN1NKX6.3 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...Continue Reading

References

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Feb 23, 2011·The Journal of Pathology·Jung Hwan YoonWon Sang Park
Mar 26, 2013·Molecular Cell·Eric L SnyderTyler Jacks
Jul 13, 2013·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Jung Hwan YoonWon Sang Park
May 23, 2014·Cancer Research and Treatment : Official Journal of Korean Cancer Association·Kyu-Won JungJin Soo Lee
Sep 23, 2014·Carcinogenesis·Jung Hwan YoonWon Sang Park

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Citations

Dec 4, 2016·Digestive Diseases and Sciences·Haijing NiuBingzhong Su
Nov 30, 2019·Cancers·Stefan Nagel, Hans G Drexler
Jan 28, 2017·Oncotarget·Filomena AltieriPaolo Arcari
Jul 20, 2019·International Journal of Oncology·Judit Alarcón-MillánGloria Fernández-Tilapa
Apr 16, 2020·Gastric Cancer : Official Journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association·Jung Hwan YoonWon Sang Park
Jan 9, 2016·Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc·Jung H YoonWon S Park
Jan 29, 2019·World Journal of Gastroenterology : WJG·Jung Hwan YoonWon Sang Park
Apr 29, 2018·Gastric Cancer : Official Journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association·Jung Hwan YoonWon Sang Park
Dec 6, 2018·Scientific Reports·Jung Hwan YoonWon Sang Park

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Datasets Mentioned

BETA
GSE27342

Methods Mentioned

BETA
immunoprecipitation
PCR
ChIP
transfection
Assay

Software Mentioned

CellQuest
BLAST

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