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EPB41L5 Mediates TGFβ-Induced Metastasis of Gastric Cancer

 Mi-Hyeon Jeong  ;  Soo-Yeon Park  ;  Seung-Hyun Lee  ;  JaeSung Seo  ;  Jung-Yoon Yoo  ;  Seung-Ho Park  ;  Mi Jeong Kim  ;  SooYeon Lee  ;  Subhin Jang  ;  Hyo-Kyoung Choi  ;  Jae Eun Lee  ;  Su-Jin Shin  ;  Kyung-Chul Choi  ;  Jae-Ho Cheong  ;  Ho-Geun Yoon 
 CLINICAL CANCER RESEARCH, Vol.25(12) : 3617-3629, 2019 
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PURPOSE: Because of disease heterogeneity, limited studies on effective chemotherapies and therapeutic agents for advanced gastric cancer are available. Erythrocyte membrane protein band 4.1-like 5 (EPB41L5) has critical roles in renal and breast cancer metastasis. However, its role in metastatic gastric cancer remains unknown. EXPERIMENTAL DESIGN: The specimens of 78 gastric cancer patients were analyzed by oligonucleotide microarray and survival analysis. In vitro experiments and metastatic mice models were used to assess the effects of EPB41L5 on gastric cancer metastasis. RESULTS: Gastric cancer patients with high EPB41L5 levels had poor prognosis and low survival rate. Further, TGFβ1-induced EPB41L5 expression promoted gastric cancer cell migration and invasion by Smad-dependent TGFβ signaling. Phospho-Smad3 recruitment to the EPB41L5 promoter was significantly inhibited by a TGFβ inhibitor. EPB41L5 overexpression increased lung metastasis of gastric cancer cells in nude mice, which was completely reversed by anti-EPB41L5 monoclonal antibody treatment. Importantly, p120-catenin knockdown abolished EPB41L5-enhanced gastric cancer cell metastasis. Anti-EPB41L5 monoclonal antibody treatment blocked the association of EPB41L5 with p120-catenin. CONCLUSIONS: TGFβ/EPB41L5/p120-catenin axis regulates gastric cancer cell metastasis, and EPB41L5 is a promising therapeutic target for advanced gastric cancer.
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1. College of Medicine (의과대학) > Dept. of Plastic and Reconstructive Surgery (성형외과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Biochemistry and Molecular Biology (생화학-분자생물학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Others (기타) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Surgery (외과학교실) > 1. Journal Papers
Yonsei Authors
Kim, Mi Jung(김미정)
Park, Soo Yeon(박수연) ORCID logo https://orcid.org/0000-0003-3743-9554
Yoo, Jung Yoon(유정윤) ORCID logo https://orcid.org/0000-0001-9366-3863
Yoon, Ho Geun(윤호근) ORCID logo https://orcid.org/0000-0003-2718-3372
Lee, Seung Hyun(이승현) ORCID logo https://orcid.org/0000-0001-7549-9430
Lee, Jae Eun(이재은)
Cheong, Jae Ho(정재호) ORCID logo https://orcid.org/0000-0002-1703-1781
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