Breakthrough in how pancreatic cancer cells ingest nutrients points to new drug target

May 13, 2013, New York University School of Medicine

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 , feature a mutated protein known as Ras that plays a central role in a complex molecular chain of events that drives 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 understood—until 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 , the tumors stopped growing and in some cases even shrank. Moreover, pancreatic cancer cells in mice featured more macropinosomes—the vesicles that transport nutrients deep into a cell—than normal .

The discovery of a "protein eating" mechanism unique to some cancer cells sets the stage for drugs that could block the engulfing process without causing collateral damage to healthy cells and suggests new ways to ferry chemotherapeutic cargo into the heart of cancer cells.

"This work offers up a completely different way to target cancer metabolism," says lead principal investigator of the study Dafna Bar-Sagi, PhD, senior vice president and vice dean for Science, chief scientific officer and professor, Department of Biochemistry and , NYU Langone Medical Center, who first identified macropinocytosis in Ras-transformed cancer cells. "It's exciting to think that we can cause the demise of some simply by blocking this nutrient delivery process."

Crucial to the team's findings is the work of Matthew G. Vander Heiden, assistant professor of biology at the David H. Koch Institute for Integrative Cancer Research at MIT and Christian Metallo, assistant professor of bioengineering at the University of California at San Diego, who characterized how Ras cells derive energy from the constituent amino acids released after protein engulfment.

Other key contributors include Craig B. Thompson, president and CEO of the Memorial Sloan-Kettering Cancer Center and Joshua D. Rabinowitz, professor of chemistry at the Lewis Sigler Institute for Integrative Genomics at Princeton University.

Explore further: Scientists find potential loophole in pancreatic cancer defenses

Related Stories

Scientists find potential loophole in pancreatic cancer defenses

March 27, 2013
Dana-Farber Cancer Institute scientists and colleagues have discovered that pancreatic cancer cells' growth and spread are fueled by an unusual metabolic pathway that someday might be blocked with targeted drugs to control ...

Studies show that pancreatic cancer can run but not always hide from the immune system

June 11, 2012
A pair of recent studies describes how pancreatic cancer cells produce a protein that attracts the body's immune cells and tricks them into helping cancer cells grow. The research, published by Cell Press in the June 12th ...

New type of molecular switch could turn up the volume on bowel cancer treatment

November 5, 2012
(Medical Xpress)—A new type of molecular switch can boost common chemotherapy drugs to destroy bowel cancer cells, according to research presented today (Monday) at the NCRI Cancer Conference in Liverpool.

Immune system can use melanoma's own proteins to kill off cancer cells

February 4, 2013
Though a small group of proteins, the family called Ras controls a large number of cellular functions, including cell growth, differentiation, and survival. And because the protein has a hand in cellular division, mutated ...

Bitter melon juice prevents pancreatic cancer in mouse models

March 12, 2013
A University of Colorado Cancer study published this week in the journal Carcinogenesis shows that bitter melon juice restricts the ability of pancreatic cancer cells to metabolize glucose, thus cutting the cells' energy ...

New mechanism for cancer progression discovered

November 27, 2012
The protein Ras plays an important role in cellular growth control. Researchers have focused on the protein because mutations in its gene are found in more than 30 percent of all cancers, making it the most prevalent human ...

Recommended for you

How cancer metastasis happens: Researchers reveal a key mechanism

January 18, 2018
Cancer metastasis, the migration of cells from a primary tumor to form distant tumors in the body, can be triggered by a chronic leakage of DNA within tumor cells, according to a team led by Weill Cornell Medicine and Memorial ...

Modular gene enhancer promotes leukemia and regulates effectiveness of chemotherapy

January 18, 2018
Every day, billions of new blood cells are generated in the bone marrow. The gene Myc is known to play an important role in this process, and is also known to play a role in cancer. Scientists from the German Cancer Research ...

These foods may up your odds for colon cancer

January 18, 2018
(HealthDay)—Chowing down on red meat, white bread and sugar-laden drinks might increase your long-term risk of colon cancer, a new study suggests.

The pill lowers ovarian cancer risk, even for smokers

January 18, 2018
(HealthDay)—It's known that use of the birth control pill is tied to lower odds for ovarian cancer, but new research shows the benefit extends to smokers or women who are obese.

Researchers develop swallowable test to detect pre-cancerous Barrett's esophagus

January 17, 2018
Investigators at Case Western Reserve University School of Medicine and University Hospitals Cleveland Medical Center have developed a simple, swallowable test for early detection of Barrett's esophagus that offers promise ...

Scientists zoom in to watch DNA code being read

January 17, 2018
Scientists have unveiled incredible images of how the DNA code is read and interpreted—revealing new detail about one of the fundamental processes of life.

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.