November 3, 2016

A DARPP role in gastric cancer

Vanderbilt researchers have discovered a link between Helicobacter pylori infection, inflammation and gastric cancer that could suggest new anti-cancer therapies.

by Sanjay Mishra

Infection with Helicobacter pylori bacterium affects almost half of the world’s population. Chronic infection with H. pylori and its associated inflammation are considered the main risk factors for the development of gastric cancer, the third leading cause of cancer-related deaths worldwide.

Previously, Wael El-Rifai, M.D., Ph.D., and colleagues had discovered that DARPP-32 protein, overexpressed in two-thirds of gastric cancers, plays a crucial role in the development of gastric cancer and resistance to anticancer drugs.

Now in a study published in the journal Gut, El-Rifai and colleagues show that H. pylori infection turns on the transcription of DARPP-32 through activation of the pro-inflammatory NF-kB transcription factor. They show that H. pylori infection helps the inflamed cells survive cell death through upregulation of DARPP-32, which could be a key component in H. pylori-mediated oncogenesis.

This study provides a novel understanding that links H. pylori infection, inflammation and gastric tumorigenesis. It could lead to development of new anti-gastric cancer therapies targeting DARPP-32.

The research was supported in part by National Institutes of Health grants CA093999, CA095103, CA068485 and DK058404.

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