E6-associated protein (E6-AP) has a dual function. It acts as an E3 ubiquitin-protein ligase enzyme and coactivator of steroid hormone receptors. It has been implicated in mammary gland development and more recently in human breast cancer, where reduced E6AP expression correlated with invasive human breast carcinomas in comparison with adjacent normal tissues. Herein we investigate the role of E6AP in breast cancer invasion and metastasis. We have discovered that E6AP can act as a suppressor of cell motility, invasiveness and metastasis. We show that loss of E6AP promotes cell migration and invasion in-vitro and in-vivo. Restoration of E6AP expression in triple negative breast cancer (TNBC) cells, impedes their invasive capacity in-vitro, and represses metastatic colonization in xenografted tumours. In search for the underlying mechanism, we found that E6AP drives actin cytoskeletal remodelling, key step for cancer invasion via regulation of RhoGTPases proteins. We show that E6AP can drive the downregulation of ECT2, a guanosine exchange factor (GEF) which catalyse the GTP loading of RhoGTPases proteins that is required for tumour cell invasion. These findings establish E6AP as a novel metastatic suppressor of breast cancer cells.