Myoferlin Is a Key Regulator of EGFR Activity in Breast Cancer

被引:60
作者
Turtoi, Andrei [1 ,2 ]
Blomme, Arnaud [1 ]
Bellahcene, Akeila [1 ]
Gilles, Christine [3 ]
Hennequiere, Vincent [1 ]
Peixoto, Paul [1 ]
Bianchi, Elettra [5 ]
Noel, Agnes [3 ]
De Pauw, Edwin [2 ]
Lifrange, Eric [4 ]
Delvenne, Philippe [5 ]
Castronovo, Vincent [1 ]
机构
[1] Univ Liege, Metastasis Res Lab, GIGA Canc, B-4000 Liege, Belgium
[2] Univ Liege, GIGA Syst Biol & Chem Biol, Dept Chem, Lab Mass Spectrometry, B-4000 Liege, Belgium
[3] Univ Liege, Lab Tumor & Dev Biol, GIGA Canc, B-4000 Liege, Belgium
[4] Univ Liege, Univ Hosp CHU, Dept Senol, B-4000 Liege, Belgium
[5] Univ Liege, Dept Anat & Pathol, Fac Med, B-4000 Liege, Belgium
关键词
MESENCHYMAL TRANSITION; SURVIVAL/CLONAL GROWTH; DEPENDENT MECHANISM; PROSTATE-CANCER; MYOBLAST FUSION; MEMBRANE-REPAIR; MUSCLE GROWTH; TUMOR-CELLS; IN-VIVO; RECEPTOR;
D O I
10.1158/0008-5472.CAN-13-1142
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Myoferlin is a member of the ferlin family of proteins that participate in plasma membrane fusion, repair, and endocytosis. While some reports have implicated myoferlin in cancer, the extent of its expression in and contributions to cancer are not well established. In this study, we show that myoferlin is overexpressed in human breast cancers and that it has a critical role in controlling degradation of the epidermal growth factor (EGF) receptor (EGFR) after its activation and internalization in breast cancer cells. Myoferlin depletion blocked EGF-induced cell migration and epithelial-to-mesenchymal transition. Both effects were induced as a result of impaired degradation of phosphorylated EGFR via dysfunctional plasma membrane caveolae and alteration of caveolin homo-oligomerization. In parallel, myoferlin depletion reduced tumor development in a chicken chorioallantoic membrane xenograft model of human breast cancer. Considering the therapeutic significance of EGFR targeting, our findings identify myoferlin as a novel candidate function to target for future drug development. Cancer Res; 73(17); 5438-48. (C) 2013 AACR.
引用
收藏
页码:5438 / 5448
页数:11
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