Low Cell Density Induced Epithelial-Mesenchymal Transition in MCF10A Cell is Regulated by Proteasome Activity

Epithelial-mesenchymal transition (EMT) is a key process in tumor progression and metastasis. Previous studies have shown that MCF10A human mammary epithelial cells undergo EMT when cultured at low cell density, but the underlying mechanism remains poorly understood. Here we show that the expression of proteasome genes and the proteasome activity increase in response to low cell density. Moreover, the proteasome inhibitor MG132 blocks EMT in sparse MCF10A cells. The transcription of E-cadherin gene is repressed in sparse MCF10A cells, but is recovered upon the treatment with MG132. While the mRNA levels of Snail and Slug are markedly elevated at low cell density, the steady state protein levels are similar between sparse and confluent cells. These results suggest that the suppression of E-cadherin gene expression in sparse MCF10A cells is likely caused by downregulation of its transcription activator(s) rather than upregulation of its repressors such as Snail and Slug. This study reveals that cell density-dependent EMT in MCF10A cells is regulated by proteasome activity.