Protein Modification Could Lead to Cancer Progression

A modification called phosphorylation made to the protein RUNX3 could potentially promote cancer progression, a recent study found.

“This study identifies a new post-translational modification to RUNX3, which provides RUNX3 with a novel role in the regulation of cell division," said first author of the study Linda Chuang, MD. “Our results suggest that frequent overexpression of Aurora Kinase in cancer may reduce RUNX3 transcription activity, leading to cell division and formation of tumors. Understanding the molecular mechanisms underlying Aurora kinase-overexpressing tumors will help in the design of targeted and personalized cancer therapy.”

RUNX3 is a tumor suppressor gene that prevents tumor formation by binding to DNA. This blocks the cell division that is essential for cancer.

Phosphorylation is the addition of a phosphate group to a molecule and is carried out by Aurora Kinase, according to a study published by Proceedings of the National Academy of Science. In certain cancers, this enzyme is present in high levels.

Phosphorylation prevents RUNX3 from binding to DNA. The protein then relocates to centrosomes, which control the beginning of cell division.

"Unlike other modifications which stem from changes to the RUNX3 DNA itself or how DNA is read, phosphorylation does not accompany any changes in the DNA and is hence undetectable at the genetic level," concluded the study’s senior principle investigator Yoshiaki Ito, MD, PhD. “Given that modifications such as phosphorylation are likely to be impermanent and reversible, the clinical implications are far-ranging. Moving forward, the team is looking into ways to assess the feasibility of enhancing RUNX tumor suppression or inhibiting RUNX mitotic function to kill rapidly proliferating cancer cells.”