The RON receptor tyrosine kinase promotes metastasis by triggering epigenetic reprogramming through the thymine glycosylase MBD4 (RNA-Seq)

ABSTRACT: Metastasis is the major cause of death in cancer patients, yet the genetic/epigenetic programs that drive metastasis are poorly understood. Here, we report a novel epigenetic reprogramming pathway that is required for breast cancer metastasis. Concerted differential DNA methylation is initiated by activation of the RON receptor tyrosine kinase by its ligand, macrophage stimulating protein (MSP). Through PI3K signaling, RON/MSP promotes expression of the G:T mismatch-specific thymine glycosylase MBD4. RON/MSP and MBD4-dependent aberrant DNA methylation results in misregulation of a specific set of genes. Knockdown of MBD4 reverses methylation at these specific loci, and blocks metastasis. We also show that the MBD4 glycosylase catalytic residue is required for RON/MSP-driven metastasis. Ana

ORGANISM(S): Homo sapiens

SUBMITTER: Cunha S 

PROVIDER: S-ECPF-GEOD-52687 | biostudies-other | 2014 Jan

REPOSITORIES: biostudies-other