FER kinase promotes breast cancer metastasis by regulating [α.sub.6]- and [β.sub.1]-integrin-dependent cell adhesion and anoikis resistance

Metastatic breast cancer cannot be treated successfully. Currently, the targeted therapies for metastatic disease are limited to human epidermal growth factor receptor 2 and hormone receptor antagonists. Understanding the mechanisms of breast cancer growth and metastasis is therefore crucial for the development of new intervention strategies. Here, we show that FER kinase (FER) controls migration and metastasis of invasive human breast cancer cell lines by regulating [α.sub.6]- and [β.sub.1]-integrin-dependent adhesion. Conversely, the overexpression of FER in non-metastatic breast cancer cells induces pro-invasive features. FER drives anoikis resistance, regulates tumour growth and is necessary for metastasis in a mouse model of human breast cancer. In human invasive breast cancer, high FER expression is an independent prognostic factor that correlates with high-grade basal/triple- negative tumours and worse overall survival, especially in lymph node-negative patients. These findings establish FER as a promising target for the prevention and inhibition of metastatic breast cancer. Oncogene (2013) 32, 5582-5592; doi: 10.1038/onc.2013.277; published online 22 July 2013 Keywords: breast cancer; cell adhesion; cell migration; FER kinase; metastasis