In:
Cancer Science, Wiley, Vol. 109, No. 6 ( 2018-06), p. 1787-1798
Abstract:
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.
Type of Medium:
Online Resource
ISSN:
1347-9032
,
1349-7006
DOI:
10.1111/cas.2018.109.issue-6
Language:
English
Publisher:
Wiley
Publication Date:
2018
detail.hit.zdb_id:
2115647-5
detail.hit.zdb_id:
2111204-6
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