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Inflammatory feedback loop promotes colorectal cancer metastasis

Induction of the epithelial-mesenchymal transition () 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 aren’t completely understood; however, evidence implicates inflammation in this process.

In this issue of the , 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 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.

Article:

IL-6R/STAT3/miR-34a feedback loop promotes EMT-mediated colorectal cancer invasion and metastasis

Accompanying commentary:

Microenvironment-dependent cues trigger miRNA-regulated feedback loop to facilitate the EMT/MET switch

Source

JCI online ahead of print, March 18, 2014

Journal of Clinical Investigation