Outwitting a brainy gene

May 1, 2012

(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.

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