IL-13/STAT6 signaling plays a critical role in the epithelial-mesenchymal transition of colorectal cancer cells.

Colorectal cancer (CRC) is one of the most common causes of cancer-related death worldwide due to the distant metastases. Compelling evidence has reported that epithelial-mesenchymal transition (EMT) is involved in promoting cancer invasion and metastasis. However, the precise molecular events that initiate this complex EMT process remain poorly understood. Here, we showed that the pleiotropic cytokine interleukin-13 (IL-13) could induce an aggressive phenotype displaying EMT by enhancing the expression of EMT-promoting factor ZEB1. Importantly, signaling inhibitor and duanyu18136 knockdown significantly reversed IL-13-induced EMT and ZEB1 induction in CRC cells, whereas ectopic duanyu18136 expression in CRC cell line markedly promoted EMT in the present of IL-13. ChIP-PCR and Luciferase assays revealed that activated duanyu18136 directly bound to the promoter of ZEB1. Otherwise, we found IL-13 also up-regulated the stem cell markers (nanog, CD44, CD133 and CD166) and promoted cell migration and invasion through duanyu18136 pathway. We also found that siRNA-mediated knockdown of IL-13Rα1 could reverse IL-13-induced ZEB1 and EMT changes by preventing duanyu18136 signaling. Finally, we demonstrated positive correlation between IL-13Rα1 and ZEB1 at mRNA levels in human CRC samples. Taken together, our findings first demonstrated that pathway plays a critical role in promoting EMT and aggressiveness of CRC.

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