title: Cancer-associated upregulation of histone H3 lysine 9 trimethylation promotes cell motility in vitro and drives tumor formation in vivo.
abstract: 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 SUV39H1 is clearly involved in regulating cell migration in vitro. Overexpression of wild-type SUV39H1, but not enzymatically inactive SUV39H1, activated migration in breast and colorectal cancer cells. Inversely, migration was reduced by knockdown of SUV39H1 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 SUV39H1 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.
authors.affiliation: Department of Molecular Pathology, Graduate School of Medicine and Health Science, Osaka University, Osaka, Japan.
authors.forename: Yuhki
authors.initials: Y
authors.lastname: Yokoyama
authors.forename: Miki
authors.initials: M
authors.lastname: Hieda
authors.forename: Yu
authors.initials: Y
authors.lastname: Nishioka
authors.forename: Ayaka
authors.initials: A
authors.lastname: Matsumoto
authors.forename: Satomi
authors.initials: S
authors.lastname: Higashi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kimura
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Yamamoto
authors.forename: Masaki
authors.initials: M
authors.lastname: Mori
authors.forename: Shuji
authors.initials: S
authors.lastname: Matsuura
authors.forename: Nariaki
authors.initials: N
authors.lastname: Matsuura
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D063646:Carcinogenesis / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics*; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D044127:Epigenesis, Genetic; D005260:Female; D000076983:Histone Methyltransferases; D011495:Histone-Lysine N-Methyltransferase / Q000235:genetics / Q000378:metabolism; D006657:Histones / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008198:Lymph Nodes / Q000378:metabolism / Q000473:pathology; D008207:Lymphatic Metastasis; D008239:Lysine / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008745:Methylation; D008780:Methyltransferases / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D006657:Histones; D012097:Repressor Proteins; C407843:SUV39H1 protein, human; D000076983:Histone Methyltransferases; D008780:Methyltransferases; D011495:Histone-Lysine N-Methyltransferase; D008239:Lysine
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