Breast tumor interleukin-6 (IL-6) levels increase with tumor grade, and elevated 
serum IL-6 correlates with poor breast cancer patient survival. 
Epithelial-mesenchymal transition (EMT) phenotypes such as impaired E-cadherin 
expression or aberrant Vimentin induction are associated with enhanced 
metastasis and unfavorable clinical outcome in breast cancer. Despite this fact, 
few tumor microenvironment-derived extracellular signaling factors capable of 
provoking such a phenotypic transition have been identified. In this study, we 
showed that IL-6 promoted E-cadherin repression among a panel of estrogen 
receptor-alpha-positive human breast cancer cells. Furthermore, ectopic stable 
IL-6 expressing MCF-7 breast adenocarcinoma cells (MCF-7(IL-6)) exhibited an EMT 
phenotype characterized by impaired E-cadherin expression and induction of 
Vimentin, N-cadherin, Snail and Twist. MCF-7(IL-6) cells formed xenograft tumors 
that displayed loss of E-cadherin, robust Vimentin induction, increased 
proliferative indices, advanced tumor grade and undifferentiated histology. 
Finally, we showed aberrant IL-6 production and STAT3 activation in MCF-7 cells 
that constitutively express Twist, a metastatic regulator and direct 
transcriptional repressor of E-cadherin. To our knowledge, this is the first 
study that shows IL-6 as an inducer of an EMT phenotype in breast cancer cells 
and implicates its potential to promote breast cancer metastasis.