William Kinlaw, an associate professor of medicine at Dartmouth Medical School, has been working on a protein called S14 since 1990. Over the past few months, however, the news about S14 has picked up. Through a series of recently published academic studies, Kinlaw and his colleagues are ready to pronounce S14 a potential drug target in treating breast cancer.
"Over the past three years, we've learned about S14 and its role in communicating information about the nutrient and energy supply to genes required for fat metabolism in breast cancer cells," says Kinlaw, who is also affiliated with the Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center. "With this knowledge has also come the understanding that most breast cancers have found a mechanism to turn on the S14 gene."
He explains that these tumors are 'addicted' to S14, because it is required for the activation of a group of genes that allow the cancer cells to make fat. Kinlaw and his team have found that breast cancer cells die if S14 is removed, and their analysis of human breast tumors indicates that S14 is critical for metastasis.
"This makes sense, as fat is a crucial fuel for breast cancers," he says. "We believe this is especially so during a tumor cell's attempt to journey from the breast to other parts of the body, because the normal breast tissue supplies machinery that allows tumor cells to acquire fat from the bloodstream. Our data support the hypothesis that once the cells leave this metabolically friendly breast environment, the ability to manufacture their own fat becomes a make-or-break issue."
These findings are supported by three recently published articles. First, a few months ago, Kinlaw and his team published a study in the February 1, 2006, issue of Experimental Cell Research that further explored S14's relationship in driving fat metabolism in breast cancer cells. The researchers discovered that if you inactivate this protein, the cancer cells die. Because of this, Kinlaw explains, S14 may be a new anticancer target for breast cancer patients.
Second, in the July 2006 issue of Breast Cancer Research and Treatment, Kinlaw and fellow Dartmouth researchers Bernard Cole, Peter Morganelli, Gary Schwartz, and Wendy Wells published a study that connected the amount of S14 present in a given clinical breast cancer case to the prediction, with surprising accuracy, of which tumors would recur on long-term follow up. The researchers used a special new antibody made at Norris Cotton Cancer Center in their predictions. Kinlaw says that this study revealed the potential of S14 as a new marker for prognosis in breast cancer, and experiments are now underway to validate this result. Kinlaw has also tapped into the expertise at Dartmouth's Tuck School of Business, where students formulated this idea as a model business plan for a class project for Gregg Fairbrothers, adjunct professor of business administration and the director of the Dartmouth Entrepreneurial Network.
And finally, the journal Endocrinology invited Kinlaw and colleagues to review the topic of fat metabolism in breast cancer cells. In the review, which was available online on June 29, the researchers present a new theory of breast cancer metastasis and its relationship to fat metabolism and diet that focuses on S14.
"We're now working to examine this idea rigorously in cancer-prone mice engineered to lack S14 in the mammary gland, and to find areas on the S14 protein that might be suitable for attack with a drug," says Kinlaw.
Kinlaw's work is supported by funding from the National Institutes of Health and the Department of Defense.
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