Transcriptional activation of EGFR by HOXB5 and its role in breast cancer cell invasion

Abstract

HOX genes are transcription factors that play important roles in body patterning and many cellular processes during embryonic, fetal, and adult development. Given their important function in normal tissues, it is reasonable to assume that abnormal expression of HOX genes in adults could lead to serious diseases such as cancer. Our previous study reported HOXB5 to be significantly up-regulated in breast cancer, and its expression was found to be associated with tumor cell proliferation and invasion. Furthermore, the epidermal growth factor receptor (EGFR), a cellular tyrosine kinase that plays an important role in breast cancer progression, was found significantly up-regulated by HOXB5 in ER-positive breast cancer cells. In the present study, we demonstrated that HOXB5 regulates EGFR expression at the transcriptional level by directly binding to its promoter region and promotes phosphorylation of EGFR as well as its downstream effectors. Patients with ER-positive breast cancer, having high co-expression of HOXB5 and EGFR, had poor prognosis than those with low expression. Knockdown studies validated a key role played by EGFR in the HOXB5-induced invasion of breast cancer cells. These results suggest that targeting EGFR could be an effective strategy to treat breast cancer in patients with high HOXB5 expression.