The molecular mechanisms of epithelial to mesenchymal transition (EMT) are essential for the migration of newborn neurons during brain development, but a defect in this process can also cause cancer metastasis. This discovery has ramifications for understanding cancer metastasis and brain development and could lead to earlier diagnosis and better treatments, according to the authors (Nature Cell Biology, August 8, 2022).

EMT enables cell migration and is vital for early development processes including brain development as well as for wound healing later in life. However, it's also used by cancer cells for metastasis. The scientists identified the protein ZNF827 as a critical regulator of EMT. The protein orchestrated a large-scale remodeling of the splicing landscape by recruiting HDAC1 for epigenetic modulation of distinct genomic loci. This slowed RNA polymerase II progression and altered the splicing of genes encoding key EMT regulators in cis.

The findings reveal an "unprecedented" complexity of crosstalk between epigenetic landscape and splicing program in governing EMT and identifies ZNF827 as a master regulator coupling these processes during EMT in brain development and breast cancer metastasis.

This discovery opens new opportunities for a therapeutic intervention against cancer and a better understanding of neurodevelopmental disorders involving defects in brain development, the authors said.