Epigenetic silencing of GDF1 disrupts SMAD signaling to reinforce gastric cancer development

Accumulating evidence reveals the effectiveness of epigenetic therapy in gastric cancer. However, the molecular mechanisms and targets underlying such therapeutic responses remain elusive. Herein, we report an aberrant yet therapeutically rectifiable epigenetic signaling in gastric carcinogenesis. A...

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Veröffentlicht in:	Oncogene 2016-04, Vol.35 (16), p.2133-2144
Hauptverfasser:	Yang, W, Mok, M T S, Li, M S M, Kang, W, Wang, H, Chan, A W, Chou, J-L, Chen, J, Ng, E K W, To, K-F, Yu, J, Chan, M W Y, Chan, F K L, Sung, J J Y, Cheng, A S L
Format:	Artikel
Sprache:	eng
Schlagworte:	13/106 13/109 13/31 13/51 13/89 13/95 631/337/176 64/60 82/80 96/63 Animals Apoptosis Azacytidine c-Myc protein Cancer Carcinogenesis Care and treatment Cell Biology Cell proliferation Cellular proteins Cellular signal transduction Development and progression DNA Methylation Epigenesis, Genetic Epigenetics Epithelial cells Gastric cancer Gene expression Gene Silencing Genetic aspects Genomes Growth Differentiation Factor 1 - genetics GTP-binding protein Health aspects Human Genetics Humans Internal Medicine Male Medical prognosis Medicine Medicine & Public Health Mice Mice, Inbred C57BL Molecular modelling Myc protein N-Methyl-N-nitrosourea Oncology original-article Phosphorylation Promoter Regions, Genetic Properties Retina Retinoblastoma Retinoblastoma protein Signal transduction Signal Transduction - genetics Smad protein Smad Proteins - metabolism Smad2 protein Stomach cancer Stomach Neoplasms - genetics Stomach Neoplasms - metabolism Stomach Neoplasms - pathology Therapeutic targets Transcription Transforming growth factor-b Transforming growth factors Tumors
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Zusammenfassung:	Accumulating evidence reveals the effectiveness of epigenetic therapy in gastric cancer. However, the molecular mechanisms and targets underlying such therapeutic responses remain elusive. Herein, we report an aberrant yet therapeutically rectifiable epigenetic signaling in gastric carcinogenesis. Administration of DNA-demethylating drug 5-aza-2′-deoxycytidine (5-aza-dC) reduced gastric cancer incidence by ~74% ( P
ISSN:	0950-9232 1476-5594
DOI:	10.1038/onc.2015.276