For a cancer cell to metastasize, it must cross the basement membrane (BM) and invade the surrounding stromal microenvironment of the primary tumour. An evolving mechanism that has been reported to contribute to the invasive behaviour of metastatic cancer cells is Epithelial to Mesenchymal Transition (EMT), a phenomenon demonstrated to occur in particular in basal-like breast tumours. Previously, we established that the more recently discovered BM protein, laminin-511 (formerly LM-10) contributes to breast cancer progression and metastasis in vitro and in vivo. Here, we used a gene knockdown approach to suppress LM-511 expression in highly metastatic 4T1.2 mammary carcinoma cells and demonstrate for the first time that the loss of tumour LM-511 dramatically impairs spontaneous metastasis to bone. We provide evidence that decreased metastasis may be mediated through modulation of epithelial to mesenchymal transition (EMT). Specifically, we found that the loss of LM-511 induced a phenotypic change towards a more epithelial-like morphology in culture and significantly reduced 4T1.2 invasive properties in vitro. Using western blot analysis, we show that these changes are associated with classical features of Mesenchymal to Epithelial Transition (MET) including increased E-cadherin and reduced N-cadherin, SNAIL1, Vimentin, ZEB1, ZEB2, and TWIST1. Furthermore we demonstrate that interaction of 4T1.2 cells with LM-511 increases their resistance to Paclitaxel and Doxorubicin. Understanding the relationship between metastasis, EMT and chemoresistance could provide promising avenues for the development of more effective therapies targeting interactions with LM-511 in chemoresistant metastatic breast cancer.