Overexpression of HACE1 in gastric cancer inhibits tumor aggressiveness by impeding cell proliferation and migration. (19th April 2018)

• Record Type: Journal Article
• Authors: Chen, Ying‐ling; Li, Dong‐ping; Jiang, Hong‐yue; Yang, Yang; Xu, Li‐li; Zhang, Shun‐cai; Gao, Hong
• Is Part Of: Cancer medicine. Volume 7:Number 6(2018:Jun.)
• Page Start: 2472
• Page End: 2484
• Publication Date: 2018-04-19
• Subjects: Gastric cancer -- HACE1 -- migration -- proliferation -- Wnt/β‐catenin pathway; 616.994005
• DOI: 10.1002/cam4.1496
• Languages: English
• ISSNs: 2045-7634

Abstract

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 β ‐catenin and inhibited the activity of the Wnt/ β ‐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/ β ‐catenin signaling pathway. Circumventing the decline of HACE1 in early stage of carcinoma may impede the tumorigenesis and malignant process of gastric cancer. Abstract : Our study observed a down‐regulation of HACE1 in gastric cancer tissues and its aberrant low expression level was significantly correlated to poor tumor pathological differentiation as well as less overall survival time of gastric cancer patients within IIIa stages. Studies, in vitro and in vivo, revealed that elevating HACE1 inhibited tumor growth and migration, and down‐regulated the wnt/ β ‐catenin pathway. In all, our studies unveiled a suppressive role of HACE1 in tumor growth and migration of gastric cancer, and it might help to provide novel insights into the blockage of tumorigenesis and malignant process of early stage of gastric cancer.