Induction of the epithelial-mesenchymal transition (EMT) in cancer cells is associated with an increased capacity to invade into surrounding tissue and migrate to distant sites. The tumor-specific factors that drive EMT aren’t completely understood; however, evidence implicates inflammation in this process.
In this issue of the Journal of Clinical Investigation, a team led by Heiko Hermeking at Ludwigs-Maximilians University determined that exposure of human colorectal cancer cells to the proinflammatory cytokine IL-6 activates the oncogenic transcription factor STAT3, which represses the gene encoding microRNA-34a (miR-34a) and promotes mesenchymal phenotypes.
The IL-6 receptor (IL-6R) was identified as a direct target of miR-34a, defining an IL-6R/STAT3/miR-34a feedback loop that promotes EMT, invasion, and metastasis. Activation of p53, which induces miR-34a, decreased IL-6-dependent invasion and migration via reduced IL-6R expression, while loss of miR-34a in a murine model of colitis-associated cancer resulted in enhanced.
In an accompanying Commentary, Raghu Kalluri and colleagues of the University of Texas MD Anderson Cancer Center discuss the role of tumor microenvironment in promoting EMT and metastasis.
JCI online ahead of print, March 18, 2014