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Cancer Res. 2013 Sep 1;73(17):5438-48. doi: 10.1158/0008-5472.CAN-13-1142. Epub 2013 Jul 17.

Myoferlin is a key regulator of EGFR activity in breast cancer.

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1
Metastasis Research Laboratory, GIGA Cancer, University of Liège, Liège, Belgium. a.turtoi@ulg.ac.be

Abstract

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.

PMID:
23864327
DOI:
10.1158/0008-5472.CAN-13-1142
[Indexed for MEDLINE]
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