Blocking the critical structure that lets cancer cells move -- their feet

Dec 16, 2010

Scientists now know that some cancer cells spread, or metastasize, throughout the body the old-fashioned way -- by using their feet. But researchers at Duke Cancer Institute have discovered a way to short-circuit their travels by preventing the development of these feet, called invadopodia. This discovery is even more important because preventing the development of these "feet" also eliminates the action of proteins present in the feet that burn through intact tissue and let cancer cells enter new cells.

The results could yield a treatment to prevent the spread of cancer, which would be taken in combination with a treatment that kills the , said Ann Marie Pendergast, Ph.D., senior author and James B. Duke Professor of Pharmacology and Cancer Biology at Duke. "A combination like this would be more effective than either treatment given alone."

"This is the first time anyone has identified the Abl family of kinases (comprising two proteins, Abl and Arg) as critical regulators of invadopodia structures," Pendergast said. "This has never been seen before."

The study was published in the on Dec. 17.

The team found that the Abl and Arg kinases are required not only for the formation and function of the invadopodia, but also that these kinases are found within these structures. "Thus, if we can find a way to block the kinases, we'll find a way to keep the feet from forming correctly and will keep the cells from moving," Pendergast said.

The researchers also made a new connection between these Abl and Arg kinases and the regulation of a Matrix Metalloproteinase (MMP) that is very important in cancer invasion and metastasis. "When you lose the functions of the Abl and Arg kinases, you also lose the function of the MMP proteins, which 'chew' through the matrix surrounding cells and tissues," Pendergast said. The MMP proteins can create openings for to escape through on their way to becoming a metastasis, she said.

The studies began because the researchers knew that Abl kinases can directly connect with actin, a filament-like protein that cells use to move. These kinases also seem to target a number of actin-regulatory proteins that are found in invadopodia, "so we thought it might be interesting to see what would happen if we blocked the activity of these kinases," Pendergast said. "We expected a mild effect, but were surprised by the striking effect we saw."

Using fluorescent proteins for imaging purposes, the team observed that when the kinase activity was blocked, the cancer cell "feet" then disappeared as well.

Pendergast said the pharmacologic agents used to block the Abl kinases are FDA-approved for use in leukemia (imatinib), which means it may not be hard to win their approval for new applications.

Explore further: Structure of sodium channels different than previously believed

Related Stories

Yale scientists map cell signaling network

Nov 30, 2005

Yale University scientists have mapped, for the first time, the proteins and kinase signaling network that control how cells of higher organisms operate.

Can cancer drugs combine forces?

Aug 16, 2007

Individuals with chronic myeloid leukemia (CML) are treated first with a drug known as imatinib (Gleevec), which targets the protein known to cause the cancer (BCR-ABL). If their disease returns, because BCR-ABL mutants emerge ...

Recommended for you

Breakthrough points to new drugs from nature

Apr 16, 2014

Researchers at Griffith University's Eskitis Institute have developed a new technique for discovering natural compounds which could form the basis of novel therapeutic drugs.

World's first successful visualisation of key coenzyme

Apr 16, 2014

Japanese researchers have successfully developed the world's first imaging method for visualising the behaviour of nicotine-adenine dinucleotide derivative (NAD(P)H), a key coenzyme, inside cells. This feat ...

User comments : 0

More news stories

Poll: Big Bang a big question for most Americans

Few Americans question that smoking causes cancer. But they have more skepticism than confidence in global warming, the age of the Earth and evolution and have the most trouble believing a Big Bang created the universe 13.8 ...

Making graphene in your kitchen

Graphene has been touted as a wonder material—the world's thinnest substance, but super-strong. Now scientists say it is so easy to make you could produce some in your kitchen.