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Pathway identified in human lymphoma points way to new blood cancer treatments
Date:11/21/2012

PHILADELPHIA A pathway called the "Unfolded Protein Response," or UPR, a cell's way of responding to unfolded and misfolded proteins, helps tumor cells escape programmed cell death during the development of lymphoma.

Research, led by Lori Hart, Ph.D., research associate and Constantinos Koumenis, Ph.D., associate professor,and research division director in the Department of Radiation Oncology, both from the Perelman School of Medicine, University of Pennsylvania, and Davide Ruggero, Ph.D., associate professor, Department of Urology, University of California, San Francisco, shows for the first time that the UPR is active in patients with human lymphomas and mice genetically bred to develop lymphomas. Importantly, when the UPR is inactivated, lymphoma cells readily undergo cell death. Their findings appear online in the Journal of Clinical Investigation and will appear in the December 2012 issue.

"The general implications of our work are that components of this pathway may be attractive anti-tumor targets, especially in lymphomas," says Koumenis. "Indeed, an enzyme called PERK, a kinase that we found to play a central role in UPR, is already being targeted by several groups, in academia and pharmaceutical companies with specific inhibitors."

The cancer-causing gene c-Myc paradoxically activates both cell proliferation and death. When the cell becomes cancerous, c-Mycinduced death is bypassed, promoting tumor formation. "A critical feature of c-Myc-overexpressing cells is an increased rate of protein synthesis that is essential for Myc's ability to cause cancer," says Tom Cunningham, Ph.D., a postdoctoral fellow in the Ruggero lab. "Myc tumor cells use this aberrant production of proteins to block apoptosis and activate the UPR. These cancer cells depend on Myc-induced increases in protein abundance to survive. Therefore, targeting protein synthesis downstream of Myc oncogenic activity may represent a promising new therape
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Contact: Karen Kreeger
karen.kreeger@uphs.upenn.edu
215-349-5658
University of Pennsylvania School of Medicine
Source:Eurekalert  

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