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How a Growth Control Path Takes a Wrong Turn to Cancer

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Science  04 Sep 1998:
Vol. 281, Issue 5382, pp. 1438-1441
DOI: 10.1126/science.281.5382.1438

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As researchers uncover the internal workings of one of the cell's key developmental and growth regulatory pathways--called the Wnt pathway after the protein that sets it in motion--they are getting a better grasp on the causes of cancer. Because activation of the Wnt pathway stimulates cell growth, researchers had long suspected that too much Wnt signaling could cause problems. The new work, described on page 1509 of this issue, provides further support for that idea, and also helps explain how the pathway malfunctioning might lead to cancer. It shows that damage to a well-known tumor suppressor gene--the adenomatous polyposis coli gene (APC), which is lost or inactivated in some 85% of colorectal cancers--can result in activation of an equally prominent oncogene--the c- MYC gene--via the Wnt pathway. Such abnormal MYC activation may in turn lead to excessive cell proliferation. Researchers are becoming optimistic that they can put these results to work developing new anticancer drugs that act by blocking c- MYC activation.