EPB41L5 Mediates TGFβ-Induced Metastasis of Gastric Cancer

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
Mi-Hyeon JeongHo-Geun Yoon

Abstract

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. 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. 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. TGFβ/EPB41L5/p120-ca...Continue Reading

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Citations

Mar 11, 2020·The Journal of Immunology : Official Journal of the American Association of Immunologists·Holly M Scott Algood
Feb 11, 2021·Journal of Experimental & Clinical Cancer Research : CR·Chenlong Song, Chongzhi Zhou

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