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Cancer growth is a long, complex, multi-stage process involving a variety of different “players.” This complexity is part of the difficulty facing cancer researchers. Meanwhile, each discovery or identification of a new “player,” or previously unknown stage in the process, offers new opportunities for blocking the disease. Recently, a team of Weizmann Institute scientists has discovered an important “player” in the development of colon cancer. The researchers – Prof. Avri Ben-Ze’ev of the Molecular Cell Biology Department and Dr. Nancy Gavert, M.D., a surgeon and current Ph.D. student, published their findings in The Journal of Cell Biology.
Prof. Ben-Ze’ev has long been studying the exact role of a gene called beta-catenin in various types of cancer. It is known that beta-catenin activates other genes, and in previous studies, Prof. Ben-Ze’ev’s group had identified several beta-catenin activated genes that are involved in the development of malignant melanoma and colon cancer. In the new research,
performed in tissue culture, the scientists discovered that colon cancer cells contain unexpectedly large quantities of a protein called L1 that is most often found in growing nerve cells. This protein, localized on cell membranes, can serve both as a lock and a key in the binding between cells: as a lock, or receptor, it can bind with other L1 molecules on the surface of like cells, and as a key that fits many locks, it can bind with different types of receptors on the membranes of other cell types.
Thanks to these abilities, L1 plays an important role in the process by which healthy nerve cells develop and find their way in the intercellular space. However, when L1 quantities in cancer cells are elevated, due to excessive beta-catenin activity, these cells become particularly invasive and deadly. Among other things, they get better at both moving around and penetrating the body’s connective tissues. L1 also renders cancerous cells more resistant to stress and helps them survive in adverse conditions. These attributes can help cancer to grow and spread. Thus, L1 protein appears to act as a strategic partner that assists in the development of colon cancer tumors.
Working in collaboration with Dr. Thomas Brabletz, a pathologist from the University of Erlangen in Germany and Dr. Peter Altevogt's group at the German Cancer Research Center in Heidelberg, Institute researchers analyzed a large number of colorectal cancer samples from human patients.
They found that L1 is present in large quantities exclusively in cancer cells from the most aggressive and invasive front of tumors and in metastases at adjacent lymph nodes. In an additional surprise finding, the scientists found concentrations of nerve cell bundles containing L1 located next to clusters of colon cancer cells that, as mentioned, boast large amounts of L1 on their surfaces. This finding of proximity, paired with the knowledge of the many attributes of L1 in tumor cell motility and invasion, may have important implications for novel ways of diagnosing colon cancer and for its therapy.
Prof. Avri Ben-Ze'ev’s research is supported by the M.D. Moross Institute for Cancer Research; the Yad Abraham Center for Cancer Diagnostics and Therapy; the Jean-Jacques Brunschwig Fund for the Molecular Genetics of Cancer; the late Mrs. Bronia Hacker, France; La Fondation Raphael et Regina Levy and the late Maria Zondek.Prof. Ben-Ze'ev is the incumbent of the Samuel Lunenfeld-Reuben Kunin Chair of Genetics.