한빛사 논문
Mi-Hyeon Jeong1, Soo-Yeon Park1, Seung-Hyun Lee1, JaeSung Seo1, Jung-Yoon Yoo1, Seung-Ho Park3, Mi Jeong Kim1, SooYeon Lee1, Subhin Jang1, Hyo-Kyoung Choi2, Jae Eun Lee4, Su-Jin Shin5, Kyung-Chul Choi3,*, Jae-Ho Cheong1,4,*, and Ho-Geun Yoon1,*
1 Department of Biochemistry and Molecular Biology, Brain Korea 21 PLUS Project for Medical Sciences, Yonsei University College of Medicine, Seoul, Korea 03722
2 Division of Nutrition and Metabolism Research Group, Korea Food Research Institute, Gyeonggi-do, Korea 13539
3 Department of Biomedical Sciences, Asan Medical Center, AMIST, University of Ulsan College of Medicine, Seoul, Korea 05505
4 Department of Surgery, Yonsei University College of Medicine, Seoul, Korea 03722
5 Department of Pathology, Hanyang University College of Medicine, Seoul, Korea
*Correspondence should be addressed to Kyung-Chul Choi, PhD, Department of Biomedical Sciences, Asan Medical Center, AMIST, University of Ulsan College of Medicine, Seoul, Korea 05505; Jae-Ho Cheong, MD, PhD, Department of Surgery, Yonsei University College of Medicine, Seoul, Korea 03722 ; or Ho-Geun Yoon, PhD, Department of Biochemistry and Molecular Biology, Yonsei University College of Medicine, Seoul, Korea 03722
Abstract
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 analysed 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, transforming growth factor (TGF)-β1-induced EPB41L5 expression promoted gastric cancer cell migration and invasion by Smad-dependent TGF-β signalling. Phospho-Smad3 recruitment to the EPB41L5 promoter was significantly inhibited by a TGF-β 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: TGF-β/EBP41L5/p120-catenin axis regulates gastric cancer cell metastasis, and EPB41L5 is a promising therapeutic target for advanced gastric cancer.
Keywords: EPB41L5, TGF-β1, p120-catenin, Gastric cancer, Metastasis
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