Outwitting a brainy gene

(Medical Xpress) -- The very first in the series of mutations causing colon cancer occurs in the beta-catenin gene; this gene is abnormally activated in about 90 percent of colorectal cancer patients, and in a much smaller percentage of people with almost every other type of cancer. Beta-catenin plays a dual role in the cell: it promotes adhesion, or stickiness, between cells, and regulates the expression of genes in the nucleus.

Research conducted in the laboratory of Prof. Avri Ben-Ze'ev of the Department of Molecular Cell Biology suggests that, in cancer, beta-catenin functions as an : when aberrantly activated, it spurs malignant transformation and causes the cell to proliferate abnormally. In one collaborative project with Institute colleagues, Prof. Ben-Ze'ev discovered that in normal cells, the gene keeps beta-catenin in check, but in , p53 loses its grip on beta-catenin. In another collaborative project, a team led by Prof. Ben-Ze'ev isolated a short peptide (protein fragment) that blocks a vital portion of the beta-catenin molecule; the protein may thwart the development of cancer by preventing beta-catenin from acting as an oncogene.

More recently, Prof. Ben-Ze'ev's team unraveled several crucial elements in the signaling chain unleashed by the corrupt beta-catenin. One of these elements is Nr-CAM, a not previously known to play a role in cancer.

In healthy people, the protein made by the Nr-CAM gene is present only in the brain and not at all in other tissues of the body, but the Weizmann scientists showed that the Nr-CAM levels are dramatically elevated in colon cancer and ; in fact, the more advanced the tumor, the higher the Nr-CAM level.

These findings could lead to the screening of large populations and early detection of cancer, based on the detection of the protein made by the Nr-CAM gene: this protein is likely to be present only in people with cancer caused by overly activated beta-catenin. Moreover, since the protein made by the Nr-CAM gene sticks out from the surface of cells, it is a convenient target for cancer therapy: by inactivating Nr-CAM, it may be possible to interrupt the chain of signals released by beta-catenin, thereby suppressing the development of prevalent malignancies such as melanoma and colon cancer.

Prof. Ben-Ze'ev's laboratory has also revealed that beta-catenin is involved in a key mechanism leading to the metastasis of colon cancer. By manipulating this mechanism, his team succeeded in reversing the metastatic properties of cells in vitro. This research raises hopes that a target-specific therapy might be devised to prevent, or reverse, the invasive behavior of metastatic cells.

add to favorites email to friend print save as pdf

Related Stories

Lithium and bone healing

Jul 30, 2007

Researchers have described a novel molecular pathway that may have a critical role in bone healing and have suggested that lithium, which affects this pathway, has the potential to improve fracture healing.

Tapeworm drug inhibits colon cancer metastasis

Jun 17, 2011

A compound that for about 60 years has been used as a drug against tapeworm infection is also apparently effective against colon cancer metastasis, as studies using mice have now shown. The compound silences a gene that triggers ...

New drug targets for squamous cell carcinoma

May 19, 2011

Researchers at Fred Hutchinson Cancer Research Center have discovered a new drug target for squamous cell carcinoma – the second most common form of skin cancer. Scientists in the laboratory of Valeri Vasioukhin, Ph.D., ...

Recommended for you

Gene test aids cancer profile

1 hour ago

The first round of chemotherapy did little to suppress Ron Bose's leukemia. The second round, with 10 times the dose, knocked the proliferating blast cells down, but only by half.

How a common antacid could lead to cheaper anti-cancer drugs

19 hours ago

A popular indigestion medication can increase survival in colorectal cancer, according to research published in ecancermedicalscience. But in fact, scientists have studied this for years - and a group of cancer advocates want t ...

User 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.