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Breakthrough in how pancreatic cancer cells ingest nutrients points to new drug target
Date:5/13/2013

In a landmark cancer study published online in Nature, researchers at NYU School of Medicine have unraveled a longstanding mystery about how pancreatic tumor cells feed themselves, opening up new therapeutic possibilities for a notoriously lethal disease with few treatment options. Pancreatic cancer kills nearly 38,000 Americans annually, making it a leading cause of cancer death. The life expectancy for most people diagnosed with it is less than a year.

Now new research reveals a possible chink in the armor of this recalcitrant disease. Many cancers, including pancreatic, lung, and colon cancer, feature a mutated protein known as Ras that plays a central role in a complex molecular chain of events that drives cancer cell growth and proliferation. It is well known that Ras cancer cells have special nutrient requirements to grow and survive. But how Ras cells cope to actually meet their extraordinary nutrient requirements has been poorly understooduntil now. In the study, led by Cosimo Commisso, a postdoctoral fellow in the Department of Biochemistry and Molecular Pharmacology at NYU School of Medicine, show for the first time how Ras cancer cells exploit a process called macropinocytosis to swallow up the protein albumin, which cells then harvest for amino acids essential for growth.

"A big mystery is how certain tumors meet their excessive nutrient demands ," says Dr. Commisso, whose work is funded in part by the Pancreatic Cancer Action Network. "We believe they accomplish this by macropinocytosis."

The findings suggest that Ras cancer cells are particularly dependent on macropinocytosis for growth and survival. When the researchers used a chemical to block the uptake of albumin via macropinocytosis in mice with pancreatic tumors, the tumors stopped growing and in some cases even shrank. Moreover, pancreatic cancer cells in mice featured more macropinosomesthe vesicles that transport nutrients deep into a cellthan normal mou
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Contact: Christopher Rucas
Christopher.Rucas@nyumc.org
212-404-3525
NYU Langone Medical Center / New York University School of Medicine
Source:Eurekalert

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