August 6, 2015

Stomach cancer cues

Vanderbilt scientists have discovered a new molecular mechanism that promotes stomach cancer development, findings that could provide new opportunities for treatment.

by Henry H. Ong

Stomach cancer is one of the most frequent cancers in the world and does not usually respond well to current treatments. Understanding how stomach cancer develops could provide new opportunities for treatment.

Reporting last month in the journal Oncogene, Wael El-Rifai, M.D., Ph.D., and colleagues have discovered a new molecular mechanism involving the protein DARPP-32 that plays a crucial role in promoting stomach cancer development.

While it was known that DARPP-32 is over-expressed in stomach cancer, until now, no one knew how DARPP-32 worked in cancer.

Experiments on cancer cells demonstrated that DARPP-32 stabilizes another protein SRp20. SRp20 then increases expression of a cell-surface glycoprotein CD44E, which in turn leads to development of stomach cancer.

Blocking DARPP-32 significantly reduced tumor growth in live mice. In addition, DARPP-32, SRp20, and CD44E were found to be overexpressed in the majority human stomach cancers.

This new understanding of how DARPP-32, SRp20, and CD44E work in stomach cancer may provide promising targets for drug development.

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

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