| RRC ID |
73744
|
| 著者 |
Yamakado N, Okuda S, Tobiume K, Uetsuki R, Ono S, Mizuta K, Nakagawa T, Aikawa T.
|
| タイトル |
Chemical inhibition of LSD1 leads to epithelial to mesenchymal transition in vitro of an oral squamous cell carcinoma OM-1 cell line via release from LSD1-dependent suppression of ZEB1.
|
| ジャーナル |
Biochem Biophys Res Commun
|
| Abstract |
The epigenetic regulation for gene expression determines cell plasticity. Oral squamous cell carcinoma (SCC) exhibits bidirectional cell plasticity, i.e. epithelial differentiation and epithelial to mesenchymal transition (EMT). The epigenetic regulator LSD1 is a histone H3-specific demethylase to which chemical inhibitors for its activity had been developed as an anti-cancer therapeutics. The bidirectional plasticity of the oral SCC cell line OM-1 had been characterized, but it remained unclear how chemical LSD1 inhibitors affect cell plasticity. Here we reported an adverse effect against cancer therapeutics, which was EMT induction in vitro by the chemical LSD1 inhibitor. The LSD1 inhibitor caused EMT-TF ZEB1 in OM-1 to undergo EMT. Furthermore, an additional EMT-TF Snail-dependent partial EMT phenotype in OM-1 progressed to complete EMT in conjunction with LSD1 inhibitor-dependent ZEB1 induction. The promotor activity of ZEB1 was up-regulated under LSD1 inhibition. The regulatory chromatin regions of ZEB1 accumulated histone H3 methylation under the chemical inhibition of LSD1. The LSD1 inhibitor also upregulates epithelial gene expression in vitro; however, the bidirectional effect of LSD1 inhibitor should be considered in cancer therapeutics.
|
| 巻・号 |
647
|
| ページ |
23-29
|
| 公開日 |
2023-3-5
|
| DOI |
10.1016/j.bbrc.2023.01.062
|
| PII |
S0006-291X(23)00094-3
|
| PMID |
36709669
|
| MeSH |
Carcinoma, Squamous Cell* / drug therapy
Carcinoma, Squamous Cell* / genetics
Cell Line, Tumor
Epigenesis, Genetic
Epithelial-Mesenchymal Transition / genetics
Gene Expression Regulation, Neoplastic
Head and Neck Neoplasms* / genetics
Histone Demethylases / metabolism
Histones / metabolism
Humans
Mouth Neoplasms* / drug therapy
Mouth Neoplasms* / genetics
Squamous Cell Carcinoma of Head and Neck / genetics
Zinc Finger E-box-Binding Homeobox 1 / genetics
Zinc Finger E-box-Binding Homeobox 1 / metabolism
|
| IF |
2.985
|
| リソース情報 |
| ヒト・動物細胞 |
293(RCB1637) |
