Breast cancer is a heterogeneous disease comprising a number of molecular subtypes. Estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) are molecular markers that are used to guide the management and treatment of breast cancer. However, triple negative breast cancers (TNBC) do not express ER and PR and do not have amplification of the HER2 gene. Therefore, they respond poorly to current hormone or HER2-targeted therapies, are more likely to develop distant metastases and are associated with a poor prognosis. Thus, identification of novel therapeutic targets is urgently needed. Here we show that the more recently discovered basement membrane protein, laminin-511 (LM-511, formerly LM-10) is expressed at high levels in TNBC and contributes to progression and metastasis. Specifically, we used a gene knockdown approach to stably suppress LM-511 expression in highly metastatic MDA-MB-231HM human carcinoma cells to demonstrate for the first time that the loss of tumour LM-511 dramatically impairs spontaneous metastasis to lungs and bone and significantly reduces the incidence of circulating tumour cells (CTCs). Further, we provide evidence that suppression of LM-511 in TNBC or adhesion to exogenous LM-511 induce morphological and functional changes consistent with Epithelial to Mesenchymal Plasticity (EMP). Using western blot analysis, we show that loss of LM-511 is associated with classical features of Mesenchymal to Epithelial Plasticity (MEP), including increased E-cadherin and reduced N-cadherin, SNAIL1, Vimentin, ZEB1, ZEB2, and TWIST1. Additionally, we demonstrate that the suppression of LM-511-binding integrin β4 receptor reduces bone metastases and shedding of CTCs. Collectively, our data demonstrates that LM-511 and its integrin β4 receptor are potential therapeutic targets for the treatment of advanced TNBC patients.