Membrane protein regulates epigenetic plasticity by mediating iron endocytosis

Reviewed by Emily Henderson, B.Sc.Aug 3 2020

CNRS researchers at the Institut Curie have recently shown that cancer cells use a membrane protein that has been known for several decades to internalize iron. Published in Nature Chemistry (August 3rd, 2020), this work shows that the absorbed iron allows cancer cells to acquire metastatic properties.

Biologists knew CD44 well, but didn't know the major biological function that it fulfils. CD44 is a glycoprotein found on the surface of many cells, in various organs, that is also involved in several biological processes: immune response, inflammation and cancer, among others. For the first time, a research team has shown that it participated in these phenomena by allowing iron to enter cells through endocytosis.

Scientists at the Laboratoire Chimie et Biologie du Cancer (CNRS/INSERM/Institut Curie) and their colleagues reached this conclusion by studying CD44's activity in cancer cells, and the resulting changes to metabolism and genetic expression.

Their results show that CD44 can internalize iron bound to hyaluronic acid. For cancer cells, the iron then fulfils two roles: it supplies the mitochondria so that it can produce metabolites necessary for the cell to pass into a metastatic state and epigenetically "unlocks" certain genes that are also necessary to the metastatic process. In that state, CD44 even becomes the main pathway for iron to enter cells.

These observations explain why CD44 was already known for its association with the appearance of metastases and relapses. But they are also surprisingbecause until now biologists thought that a different mechanism was involved in iron endocytosis, involving transferrin and its TfR1 receptor. The research team now hopes to develop molecules capable of blocking cellular iron traffic to eliminate cells with high metastatic potential.