Open AccessCancer‐associated upregulation of histone H3 lysine 9 trimethylation promotes cell motility in vitro and drives tumor formation in vivo
Author(s) -
Yokoyama Yuhki,
Hieda Miki,
Nishioka Yu,
Matsumoto Ayaka,
Higashi Satomi,
Kimura Hiroshi,
Yamamoto Hirofumi,
Mori Masaki,
Matsuura Shuji,
Matsuura Nariaki
Publication year - 2013
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.12166
Subject(s) - cancer research , histone h3 , histone methyltransferase , biology , cancer , carcinogenesis , colorectal cancer , epigenetics , ezh2 , metastasis , histone , prc2 , genetics , gene
Global histone modification patterns correlate with tumor phenotypes and prognostic factors in multiple tumor types. Recent studies suggest that aberrant histone modifications play an important role in cancer. However, the effects of global epigenetic rearrangements on cell functions remain poorly understood. In this study, we show that the histone H3 lysine 9 (H3K9) methyltransferase SUV 39H1 is clearly involved in regulating cell migration in vitro . Overexpression of wild‐type SUV 39H1, but not enzymatically inactive SUV 39H1, activated migration in breast and colorectal cancer cells. Inversely, migration was reduced by knockdown of SUV 39H1 or chemical inhibition by chaetocin. In addition, H3K9 trimethylation (H3K9me3) was specifically increased in invasive regions of colorectal cancer tissues. Moreover, the presence of H3K9me3 positively correlated with lymph node metastasis in colorectal cancer patients. Furthermore, overexpression of SUV 39H1 drove tumorigenesis in mouse, resulting in a considerable decrease in survival rate. These data indicate that H3K9 trimethylation plays an important role in human colorectal cancer progression, possibly by promoting collective cell invasion.