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 significa...
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| Format: | Article |
| Language: | English |
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Wiley
2018-06-01
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| Series: | Cancer Medicine |
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| Online Access: | https://doi.org/10.1002/cam4.1496 |
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| author | Ying‐ling Chen Dong‐ping Li Hong‐yue Jiang Yang Yang Li‐li Xu Shun‐cai Zhang Hong Gao |
| author_facet | Ying‐ling Chen Dong‐ping Li Hong‐yue Jiang Yang Yang Li‐li Xu Shun‐cai Zhang Hong Gao |
| author_sort | Ying‐ling Chen |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-ea997cbcc78745eea18abc047c18b56f |
| institution | OA Journals |
| issn | 2045-7634 |
| language | English |
| publishDate | 2018-06-01 |
| publisher | Wiley |
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| series | Cancer Medicine |
| spelling | doaj-art-ea997cbcc78745eea18abc047c18b56f2025-08-20T02:38:17ZengWileyCancer Medicine2045-76342018-06-01762472248410.1002/cam4.1496Overexpression of HACE1 in gastric cancer inhibits tumor aggressiveness by impeding cell proliferation and migrationYing‐ling Chen0Dong‐ping Li1Hong‐yue Jiang2Yang Yang3Li‐li Xu4Shun‐cai Zhang5Hong Gao6Department of Gastroenterology Zhongshan Hospital Fudan University Shanghai 200032 ChinaDepartment of Gastroenterology Zhongshan Hospital Fudan University Shanghai 200032 ChinaDepartment of Gastroenterology Zhongshan Hospital Fudan University Shanghai 200032 ChinaInstitute of Biochemistry and Cell Biology Shanghai Institutes for Biological Sciences Chinese Academy of Sciences Shanghai 200031 ChinaDepartment of Gastroenterology Zhongshan Hospital Fudan University Shanghai 200032 ChinaDepartment of Gastroenterology Zhongshan Hospital Fudan University Shanghai 200032 ChinaDepartment of Gastroenterology Zhongshan Hospital Fudan University Shanghai 200032 ChinaAbstract 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.https://doi.org/10.1002/cam4.1496Gastric cancerHACE1migrationproliferationWnt/β‐catenin pathway |
| spellingShingle | Ying‐ling Chen Dong‐ping Li Hong‐yue Jiang Yang Yang Li‐li Xu Shun‐cai Zhang Hong Gao Overexpression of HACE1 in gastric cancer inhibits tumor aggressiveness by impeding cell proliferation and migration Cancer Medicine Gastric cancer HACE1 migration proliferation Wnt/β‐catenin pathway |
| title | Overexpression of HACE1 in gastric cancer inhibits tumor aggressiveness by impeding cell proliferation and migration |
| title_full | Overexpression of HACE1 in gastric cancer inhibits tumor aggressiveness by impeding cell proliferation and migration |
| title_fullStr | Overexpression of HACE1 in gastric cancer inhibits tumor aggressiveness by impeding cell proliferation and migration |
| title_full_unstemmed | Overexpression of HACE1 in gastric cancer inhibits tumor aggressiveness by impeding cell proliferation and migration |
| title_short | Overexpression of HACE1 in gastric cancer inhibits tumor aggressiveness by impeding cell proliferation and migration |
| title_sort | overexpression of hace1 in gastric cancer inhibits tumor aggressiveness by impeding cell proliferation and migration |
| topic | Gastric cancer HACE1 migration proliferation Wnt/β‐catenin pathway |
| url | https://doi.org/10.1002/cam4.1496 |
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