Open AccessHigh G2 and S‐phase expressed 1 expression promotes acral melanoma progression and correlates with poor clinical prognosis
Author(s) -
Xu Tianxiao,
Ma Meng,
Chi Zhihong,
Si Lu,
Sheng Xinan,
Cui Chuanliang,
Dai Jie,
Yu Sifan,
Yan Junya,
Yu Huan,
Wu Xiaowen,
Tang Huan,
Yu Jiayi,
Kong Yan,
Guo Jun
Publication year - 2018
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.13607
Subject(s) - ectopic expression , gene knockdown , cancer research , metastasis , epithelial–mesenchymal transition , downregulation and upregulation , melanoma , cell growth , cell migration , medicine , biology , in vivo , tumor progression , effector , cell culture , cancer , immunology , gene , biochemistry , genetics , microbiology and biotechnology
G2 and S‐phase expressed 1 ( GTSE 1) regulates cell cycle progression in human cancers. However, its significance and mechanism of action in acral melanoma ( AM ) remain unknown. In the present study, we found that GTSE 1 expression was upregulated in advanced stage/metastatic AM tissues and metastatic cell lines, and correlated with higher stage ( P = .028) and poor disease‐free survival ( DFS ) in patients with AM ( P = .003). Cox regression assays validated GTSE 1 expression to be an independent prognostic factor of DFS for patients with AM ( P = .004). Ectopic expression of GTSE 1 enhanced primary AM cell proliferation, invasion, and migration. Loss‐of‐function in GTSE 1 attenuated metastatic AM cell proliferation and metastatic ability in vitro and in vivo. We additionally observed that inhibition of migration and invasion occurred concomitantly with a GTSE 1 knockdown‐mediated increase in E‐cadherin and decreases in N‐cadherin and Slug. We further showed that integrin subunit alpha 2 ( ITGA 2) interacts with GTSE 1 and is a downstream effector of GTSE 1. Further, ITGA 2 levels were positively correlated with GTSE 1 expression in human AM tissues. Ectopic ITGA 2 expression rescued si GTSE 1‐mediated inhibition of migration and invasion, thereby restoring epithelial‐to‐mesenchymal transition ( EMT ). In conclusion, GTSE 1 expression promotes AM progression and correlates with clinical outcomes of patients with AM , and may represent a promising therapeutic target to suppress AM progression.