RRC ID |
56094
|
著者 |
Kiuchi J, Komatsu S, Imamura T, Nishibeppu K, Shoda K, Arita T, Kosuga T, Konishi H, Shiozaki A, Kubota T, Okamoto K, Fujiwara H, Ichikawa D, Tsuda H, Otsuji E.
|
タイトル |
Overexpression of YEATS4 contributes to malignant outcomes in gastric carcinoma.
|
ジャーナル |
Am J Cancer Res
|
Abstract |
YEATS domain containing 4 (YEATS4) has functions of chromatin modification and transcriptional regulation and is in a gene-amplified region (12q13) in various human cancers. In this study, we tested whether YEATS4 acts as a cancer-promoting gene through its activation/overexpression in gastric cancer (GC). We analyzed 5 GC cell lines and 135 primary tumor samples of GC, which were curatively resected in our hospital. Overexpression of the YEATS4 protein was frequently detected in GC cell lines (5/5 cell lines, 100%) and primary GC tumor tissues (32/135 cases, 23.7%). Knockdown of YEATS4 inhibited proliferation, migration and invasion of GC cells through NOTCH2 down-regulation in a TP53 mutation-independent manner, and induced apoptosis in wild-type TP53 GC cells. Moreover, knockdown of YEATS4 improved chemosensitivity for CDDP and L-OHP. Overexpression of YEATS4 protein significantly correlated with more aggressive lymphatic invasion, larger tumor size, deeper tumor depth, positive lymph node metastasis and recurrence. Patients with YEATS4-overexpressing tumors had a lower overall survival rate than those with non-expressing tumors. Multivariate analysis demonstrated that YEATS4 was independently associated with poor outcomes. These findings suggest that YEATS4 plays a pivotal role in tumor malignant potential through its overexpression and highlight its usefulness as a prognostic factor and potential therapeutic target in GC.
|
巻・号 |
8(12)
|
ページ |
2436-2452
|
公開日 |
2018-12-1
|
PMID |
30662802
|
PMC |
PMC6325477
|
IF |
4.737
|
引用数 |
3
|
リソース情報 |
ヒト・動物細胞 |
NUGC-4(RCB1939)
HGC-27(RCB0500)
MKN7(RCB0999)
MKN45(RCB1001) |