Ring finger protein 43 associates with gastric cancer progression and attenuates the stemness of gastric cancer stem-like cells via the Wnt-β/catenin signaling pathway
Abstract Background Ring finger protein 43 (RNF43) is a member of the transmembrane E3 ubiquitin ligase family that was originally found in stem cells and plays important roles in tumor formation and progression. Our previous study indicated that RNF43 might be a tumor suppressor protein in gastric...
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doaj-059ea7501c7d49879484a4ffc61b16a42020-11-25T00:09:20ZengBMCStem Cell Research & Therapy1757-65122017-04-018111110.1186/s13287-017-0548-8Ring finger protein 43 associates with gastric cancer progression and attenuates the stemness of gastric cancer stem-like cells via the Wnt-β/catenin signaling pathwayYunhe Gao0Aizhen Cai1Hongqing Xi2Jiyang Li3Wei Xu4Yanmei Zhang5Kecheng Zhang6Jianxin Cui7Xiaosong Wu8Bo Wei9Lin Chen10Department of General Surgery, Chinese PLA General HospitalDepartment of General Surgery, Chinese PLA General HospitalDepartment of General Surgery, Chinese PLA General HospitalDepartment of General Surgery, Chinese PLA General HospitalSchool of Medicine, Tsinghua UniversitySchool of Medicine, Tsinghua UniversityDepartment of General Surgery, Chinese PLA General HospitalDepartment of General Surgery, Chinese PLA General HospitalDepartment of General Surgery, Chinese PLA General HospitalDepartment of General Surgery, Chinese PLA General HospitalDepartment of General Surgery, Chinese PLA General HospitalAbstract Background Ring finger protein 43 (RNF43) is a member of the transmembrane E3 ubiquitin ligase family that was originally found in stem cells and plays important roles in tumor formation and progression. Our previous study indicated that RNF43 might be a tumor suppressor protein in gastric cancer. Given its antagonistic relationship with leucine-rich repeat-containing G-protein-coupled receptor 5 (Lgr5), one of the gastric cancer stem cell markers, investigation of the potential role of RNF43 in gastric stem cancer cells is necessary. Methods Immunohistochemistry staining, western blot analysis, and quantitative reverse transcription polymerase chain reaction were used to determine the mRNA and protein expression level of RNF43 and other Wnt pathway factors. Gastric cancer stem-like cells were obtained from gastric cancer tumor and cell lines by tumorsphere culture. The adeno-associated virus system was used to upregulate RNF43 expression in cancer cells. Functional experiments including tumorsphere formation, chemotherapy resistance, surface marker detection, and tumor xenograft assay were performed to measure stem-like properties in gastric cancer stem-like cells after RNF43 overexpression. Results RNF43 loss was significantly associated with TNM stage, distant metastasis, and Lauren classification, and predicted worse prognosis in gastric cancer patients. RNF43 expression was even lower in tumorspheres derived from tumor tissues or cell lines compared with adherent cancer cells and normal gastric cells. Overexpression of RNF43 in gastric cancer cells impaired their stem-like properties, including sphere formation ability, chemoresistance in vitro, and tumorigenicity in vivo. Moreover, Wnt pathway-related proteins were decreased in RNF43-overexpressing cells, while Wnt pathway activators could reverse the trend to some extent. Conclusions Our findings indicated that RNF43 might not only participate in gastric cancer progression, but also attenuate the stemness of gastric cancer stem-like cells through the Wnt/β-catenin pathway.http://link.springer.com/article/10.1186/s13287-017-0548-8Ring finger protein 43Gastric cancerStem cellsStem-like property |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Yunhe Gao Aizhen Cai Hongqing Xi Jiyang Li Wei Xu Yanmei Zhang Kecheng Zhang Jianxin Cui Xiaosong Wu Bo Wei Lin Chen |
spellingShingle |
Yunhe Gao Aizhen Cai Hongqing Xi Jiyang Li Wei Xu Yanmei Zhang Kecheng Zhang Jianxin Cui Xiaosong Wu Bo Wei Lin Chen Ring finger protein 43 associates with gastric cancer progression and attenuates the stemness of gastric cancer stem-like cells via the Wnt-β/catenin signaling pathway Stem Cell Research & Therapy Ring finger protein 43 Gastric cancer Stem cells Stem-like property |
author_facet |
Yunhe Gao Aizhen Cai Hongqing Xi Jiyang Li Wei Xu Yanmei Zhang Kecheng Zhang Jianxin Cui Xiaosong Wu Bo Wei Lin Chen |
author_sort |
Yunhe Gao |
title |
Ring finger protein 43 associates with gastric cancer progression and attenuates the stemness of gastric cancer stem-like cells via the Wnt-β/catenin signaling pathway |
title_short |
Ring finger protein 43 associates with gastric cancer progression and attenuates the stemness of gastric cancer stem-like cells via the Wnt-β/catenin signaling pathway |
title_full |
Ring finger protein 43 associates with gastric cancer progression and attenuates the stemness of gastric cancer stem-like cells via the Wnt-β/catenin signaling pathway |
title_fullStr |
Ring finger protein 43 associates with gastric cancer progression and attenuates the stemness of gastric cancer stem-like cells via the Wnt-β/catenin signaling pathway |
title_full_unstemmed |
Ring finger protein 43 associates with gastric cancer progression and attenuates the stemness of gastric cancer stem-like cells via the Wnt-β/catenin signaling pathway |
title_sort |
ring finger protein 43 associates with gastric cancer progression and attenuates the stemness of gastric cancer stem-like cells via the wnt-β/catenin signaling pathway |
publisher |
BMC |
series |
Stem Cell Research & Therapy |
issn |
1757-6512 |
publishDate |
2017-04-01 |
description |
Abstract Background Ring finger protein 43 (RNF43) is a member of the transmembrane E3 ubiquitin ligase family that was originally found in stem cells and plays important roles in tumor formation and progression. Our previous study indicated that RNF43 might be a tumor suppressor protein in gastric cancer. Given its antagonistic relationship with leucine-rich repeat-containing G-protein-coupled receptor 5 (Lgr5), one of the gastric cancer stem cell markers, investigation of the potential role of RNF43 in gastric stem cancer cells is necessary. Methods Immunohistochemistry staining, western blot analysis, and quantitative reverse transcription polymerase chain reaction were used to determine the mRNA and protein expression level of RNF43 and other Wnt pathway factors. Gastric cancer stem-like cells were obtained from gastric cancer tumor and cell lines by tumorsphere culture. The adeno-associated virus system was used to upregulate RNF43 expression in cancer cells. Functional experiments including tumorsphere formation, chemotherapy resistance, surface marker detection, and tumor xenograft assay were performed to measure stem-like properties in gastric cancer stem-like cells after RNF43 overexpression. Results RNF43 loss was significantly associated with TNM stage, distant metastasis, and Lauren classification, and predicted worse prognosis in gastric cancer patients. RNF43 expression was even lower in tumorspheres derived from tumor tissues or cell lines compared with adherent cancer cells and normal gastric cells. Overexpression of RNF43 in gastric cancer cells impaired their stem-like properties, including sphere formation ability, chemoresistance in vitro, and tumorigenicity in vivo. Moreover, Wnt pathway-related proteins were decreased in RNF43-overexpressing cells, while Wnt pathway activators could reverse the trend to some extent. Conclusions Our findings indicated that RNF43 might not only participate in gastric cancer progression, but also attenuate the stemness of gastric cancer stem-like cells through the Wnt/β-catenin pathway. |
topic |
Ring finger protein 43 Gastric cancer Stem cells Stem-like property |
url |
http://link.springer.com/article/10.1186/s13287-017-0548-8 |
work_keys_str_mv |
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