Inhibition of STAT5a by Naa10p contributes to decreased breast cancer metastasis.

ABSTRACT

N-α-Acetyltransferase 10 protein (Naa10p, also called arrest-defective 1), the catalytic subunit of N-acetyltransferase A, is a critical regulator of cell death and proliferation. Naa10p is also shown to regulate cancer metastasis by inhibiting cell motility; however, its role in cancer metastasis is not fully understood. In this study, we found that high expression of Naa10p is positively correlated with the survival of patients with breast cancer, whereas negatively correlated with lymph node metastasis. Naa10p inhibits breast cancer cell migration and invasion in vitro and decreases the xenograft growth and metastasis in nude mice. Microarray screening revealed that Naa10p downregulates inhibitors of differentiation 1 (ID1) expression. Naa10p binds to signal transducer and activator of transcription 5a (STAT5a) and decreases STAT5a-stimulated ID1 expression in an acetyltransferase-independent manner. Moreover, Naa10p antagonizes Janus kinase 2-STAT5a signaling by lowering p65-activated interleukin-1ß expression. Our results demonstrate a novel mechanism through which Naa10p inhibits the metastasis of breast cancer cells by targeting STAT5a.