Epithelial-to-mesenchymal transition and iron metabolism

Epigenetic regulation of the epithelial-to-mesenchymal transition in breast cancer

R Rodriguez

Background: The epithelial-to-mesenchymal transition (EMT) denotes the shift of a group of epithelial cells to a mesenchymal form. In the epithelium polarized cells are linked by connections. In mesenchyme the cells are no longer linked to one another but they make up a support tissue attached to the extracellular matrix and the cells can migrate. Cells in EMT lose their cell-to-cell adhesion and acquire new adhesive properties towards the extracellular matrix. This process can be reversible (MET).

The paradigm of cancer stem-like cells defines the existence of cells capable of renewing themselves and disseminating. They establish themselves in new tissues and promote the formation of metastases. Cancer stem-like cells are able to carry out an epithelial-to-mesenchymal transition. It’s also been demonstrated that these cells are refractory to treatments.

The team has recently perfected a molecule called Ironomycine that can destroy cancer stem-like cells by sequestering cytoplasmic iron in small organelles called lysosomes.

Hypothesis: Iron homeostasis is involved in epigenetic plasticity in cancer cells and regulates the epithelial-to-mesenchymal transition (via an oxidative mechanism based on histone demethylation).

Objective: Understanding underlying epigenetic mechanisms should contribute to the development of this original therapeutic approach based on iron metabolism.