Epidermal growth factor induces the initiation of epithelial mesenchymal transition in high-density colorectal cancer cell culture.

Abstract

Epithelial-mesenchymal transition (EMT) is a step in the process through which colorectal cancer cells metastasize by gaining the cellular mobility associated with mesenchymal cells. However, whether the EMT occurs in cells tightly bound to each other remains largely unknown. In this study, we examined the dual influence of intercellular contact and epidermal growth factor (EGF) signaling on the induction of EMT in SW480 human colon carcinoma cells. Stimulation of densely cultured SW480 cells with EGF initiated partial EMT, following which E-cadherin levels were reduced. In these cells, the transcriptional repression of E-cadherin was caused by ZEB1 binding to its promoter region. EGF signaling did not directly induce ZEB1 mRNA upregulation but contributed to ZEB1 protein stability by regulating proteasomal degradation. Our findings indicate that EGF can induce EMT in colorectal cancer cells in the presence of cell-cell contact and may be a potential therapeutic target for metastasis.