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Overexpression of HACE1 in gastric cancer inhibits tumor aggressiveness by impeding cell proliferation and migration.


ABSTRACT: HACE1 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 HACE1 played in gastric tumorigenesis and its potential mechanism. HACE1'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-IIIa, those with lower HACE1 protein level had poorer overall survival (P = 0.025). Studies, in vivo and in vitro, showed that overexpressing HACE1 inhibited tumor proliferation and migration, and enhanced cell apoptosis. Besides, ectopic expression of HACE1 down-regulated the protein level of ?-catenin and inhibited the activity of the Wnt/?-catenin signaling pathway. All the cellular functions were abolished when we overexpressed inactive HACE1-deltaHECT. Above all, we demonstrated that HACE1 E3 ligase played a suppressive role in gastric tumorigenesis and inhibited the activity of the Wnt/?-catenin signaling pathway. Circumventing the decline of HACE1 in early stage of carcinoma may impede the tumorigenesis and malignant process of gastric cancer.

SUBMITTER: Chen YL 

PROVIDER: S-EPMC6010910 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature

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Overexpression of HACE1 in gastric cancer inhibits tumor aggressiveness by impeding cell proliferation and migration.

Chen Ying-Ling YL   Li Dong-Ping DP   Jiang Hong-Yue HY   Yang Yang Y   Xu Li-Li LL   Zhang Shun-Cai SC   Gao Hong H  

Cancer medicine 20180419 6


HACE1 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 HACE1 played in gastric tumorigenesis and its potential mechanism. HACE1'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 gastri  ...[more]

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