The researchers, headed by Prof. Avri Ben-Ze'ev of the Molecular Cell Biology Department, have confirmed that the invasive behavior of colon cancer cells results from the malfunction of adhesion-related ("cell-gluing") mechanisms.
Cells are held together by "adhesive molecules," including two key molecules called beta-catenin and E-cadherin, which are found near the surfaces of cells. Beta-catenin also has another function: when inside the nuclei of cells, it regulates the expression of genes. Beta-catenin is known to be involved in various cancers, including colon cancer, by aberrantly activating genes whose identity is mostly unclear. In previous research, Ben-Ze'ev's team identified several such genes that are involved in the progression of human melanoma and colon cancer.
Now, the scientists have found that when a colon cancer cell becomes metastatic, abnormally large amounts of beta-catenin are found in its nucleus and, unexpectedly, they bring about a reduction in adhesion. The cell can thus break loose from the tissue and migrate to form another tumor at a distant site.
Beta-catenin in the nucleus does this by activating a gene called Slug. Slug inhibits the production of beta-catenin's partner in cell adhesion, E-cadherin. The shortage of E-cadherin prevents the cell from adhering to adjacent cells. The cell takes on a boat-like shape and, leaving the pack, invades neighboring tissues until it enters the bloodstream. This mi
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American Committee for the Weizmann Institute of Science
5-Jan-2004