RRC ID 56094
Author 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.
Title Overexpression of YEATS4 contributes to malignant outcomes in gastric carcinoma.
Journal 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.
Volume 8(12)
Pages 2436-2452
Published 2018
PMID 30662802
PMC PMC6325477
Human and Animal Cells NUGC-4(RCB1939) HGC-27(RCB0500) MKN7(RCB0999) MKN45(RCB1001)