'Jekyll-and-Hyde' protein may be the key to stopping cancer metastasis

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Published September 26, 2013

| FoxNews.com

One of the deadliest aspects of a cancerous tumor is its ability to grow and spread, assimilating and destroying healthy cells throughout the body.  Controlling this lethal expansion, known as metastasis can be a difficult endeavor. But now, researchers have revealed that a notoriously fickle protein may be the key to stopping cancer’s rapid development.

Displaying ‘mood swings’ that researchers compare to those of Dr. Jekyll and Mr. Hyde, the protein E2F sometimes boosts tumor cell growth and at other times suppresses it.  According to the researchers at Oxford University who discovered E2F, they have found a way to block the abnormal protein’s change into the deadly “Mr. Hyde” – a move that results in cancer cell death.

In a study published in the journal Molecular Cell, the researchers explained E2F’s dual nature for the first time and how it can be an extremely effective target for new cancer treatments.

“We discovered this protein originally in the early 1990s, and since then we’ve discovered quite a lot (about it),” study author Nick La Thangue, a professor in the department of oncology at Oxford, told FoxNews.com.  “It’s a target, regulated by a tumor suppressor gene… and the pathway has been shown to be abnormal in virtually all tumor cells, which drives the proliferation forward.”

According to La Thangue, when E2F is functioning properly, it is a crucial tool for cell regulation.  As Mr. Hyde, the protein helps healthy cells grow, but when a cell becomes damaged or sick, the protein reverts to Dr. Jekyll and signals for the cell to die.  This process is called apoptosis, and it helps to prevent the buildup of DNA errors or the development of cancer.

However, when cancer cells do start to grow in the body, the gene that encodes E2F becomes mutated, and the protein loses its ability to foster cell death. Instead, it remains permanently in its “Mr. Hyde” state, enhancing the cancer cells’ ability to flourish.  La Thangue noted that while E2F is found in all cells of the body, tumor cells have much larger amounts of the protein.

In their study, the researchers explained that E2F’s double nature is controlled by two slightly different enzymes.

“It’s an enzyme modification, and it’s quite an unusual modification called arginine methylation,” La Thangue said. “It’s actually quite amazing stuff, because there are two different types of arginine methylation, and they differ by a small amount of chemistry.  One form provides a (molecular label) that makes the cell proliferate, and the other makes it die.”

The enzymes attach these molecular labels on different part of E2F, and they act as flags that either signal cell proliferation or signal cell death.  In cancer cells, the enzyme responsible for cell proliferation is hyperactive and ultimately overpowers the enzyme for cell death.

Upon understanding this biological mechanism, La Thangue said he and his colleagues have identified drug compounds that target the overactive enzyme, which he hopes to use to develop an effective new chemotherapy treatment for the future.

“We have a program aimed at developing small molecule drugs that target this enzyme,” La Thangue said.  “While it’s not coming out tomorrow, at the same time, it’s not 10 years away.  I’d say we’re a few years away until we move to clinical trial.”

La Thangue is confident that this new drug could be extremely beneficial for patients, as it could finally control metastasis in nearly all cancers.

“One of the beauties of this is that it’s a pathway which is abnormal in the vast majority of human tumors,” La Thangue said.  “It’s not tumor cell specific; it’s very generic.”

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http://www.foxnews.com/health/2013/09/26/jekyll-and-hyde-protein-may-be-key-to-stopping-cancer-metastasis/