MentallyHealth.Org

Researchers discover mechanism linking H. pylori infection and stomach cancer

May 13, 2017

Further tests revealed that CagA and RUNX3 physically interact with each other in human epithelial cells. The researchers found that a newly identified domain within CagA, the WW domain, recognizes a sequence in the RUNX3 protein known as the "PY motif." They further showed that this interaction leads to the "tagging" of RUNX3 for degradation via a process called ubiquitination.

Previous studies found that there are several unique sequences within the carboxyl-terminal region of CagA that are vital to the protein's ability to interact with host proteins and disrupt normal cellular processes.

"This is the first time anybody has identified a unique domain within the amino-terminal region of the CagA protein, and it will help us to better understand how this oncogenic protein functions," Chen said. "This study has uncovered a new step in the initiation of H. pylori-induced gastric cancer."

The accumulation of many deleterious changes in cells leads to the development of cancer. RUNX3 helps cells react when cellular processes go awry, so H. pylori-induced degradation of RUNX3 "could produce conditions in which aberrant cellular changes are less inhibited," Chen said.

Chen's group is working to identify the molecular mechanism by which CagA targets RUNX3 for degradation. He and his colleagues hope to design small molecules that can specifically inhibit the interaction between RUNX3 and CagA and block the degradation of RUNX3. Such drugs may be used to prevent the gastric diseases induced by H. pylori.

Source: University of Illinois at Urbana-Champaign