Large intervening non-coding RNAs (lincRNAs) are pervasively transcribed in the 
genome yet their potential involvement in human disease is not well understood. 
Recent studies of dosage compensation, imprinting, and homeotic gene expression 
suggest that individual lincRNAs can function as the interface between DNA and 
specific chromatin remodelling activities. Here we show that lincRNAs in the HOX 
loci become systematically dysregulated during breast cancer progression. The 
lincRNA termed HOTAIR is increased in expression in primary breast tumours and 
metastases, and HOTAIR expression level in primary tumours is a powerful 
predictor of eventual metastasis and death. Enforced expression of HOTAIR in 
epithelial cancer cells induced genome-wide re-targeting of Polycomb repressive 
complex 2 (PRC2) to an occupancy pattern more resembling embryonic fibroblasts, 
leading to altered histone H3 lysine 27 methylation, gene expression, and 
increased cancer invasiveness and metastasis in a manner dependent on PRC2. 
Conversely, loss of HOTAIR can inhibit cancer invasiveness, particularly in 
cells that possess excessive PRC2 activity. These findings indicate that 
lincRNAs have active roles in modulating the cancer epigenome and may be 
important targets for cancer diagnosis and therapy.