Open AccessOverexpression of HACE 1 in gastric cancer inhibits tumor aggressiveness by impeding cell proliferation and migration
Author(s) -
Chen Yingling,
Li Dongping,
Jiang Hongyue,
Yang Yang,
Xu Lili,
Zhang Shuncai,
Gao Hong
Publication year - 2018
Publication title -
cancer medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.403
H-Index - 53
ISSN - 2045-7634
DOI - 10.1002/cam4.1496
Subject(s) - carcinogenesis , wnt signaling pathway , cancer research , cancer , cell growth , apoptosis , ectopic expression , ubiquitin ligase , biology , medicine , signal transduction , chemistry , microbiology and biotechnology , cell culture , ubiquitin , biochemistry , genetics , gene
HACE 1 E3 ligase was discovered to be down‐regulated in several cancers while its role in regulating tumors was merely understood. This study aimed to explore the specific effect of HACE 1 played in gastric tumorigenesis and its potential mechanism. HACE 1's expression was found significantly lower in gastric cancer tissues compared with the adjacent normal tissues ( P < 0.001). Its protein level in gastric cancer negatively correlated to tumor pathological differentiation ( P = 0.019). And in gastric cancer patients with TNM I‐ III a, those with lower HACE 1 protein level had poorer overall survival ( P = 0.025). Studies, in vivo and in vitro, showed that overexpressing HACE 1 inhibited tumor proliferation and migration, and enhanced cell apoptosis. Besides, ectopic expression of HACE 1 down‐regulated the protein level of β ‐catenin and inhibited the activity of the Wnt/ β ‐catenin signaling pathway. All the cellular functions were abolished when we overexpressed inactive HACE 1‐delta HECT . Above all, we demonstrated that HACE 1 E3 ligase played a suppressive role in gastric tumorigenesis and inhibited the activity of the Wnt/ β ‐catenin signaling pathway. Circumventing the decline of HACE 1 in early stage of carcinoma may impede the tumorigenesis and malignant process of gastric cancer.