New research suggests that a rare sugar found in seaweed, mushrooms, seeds, and other foods may be helpful when treating skin cancer. The L-fucose sugar has been formerly associated with a number of pathological conditions like inflammation and certain types of cancer but the current study is the first to connect L-fucose with melanoma, one of the most damaging types of skin cancers.
The study titled “The transcription factor ATF2 promotes melanoma metastasis by suppressing protein fucosylation” and published in Science Signaling, was led by scientists at Sanford Burnham Prebys Medical Discovery Institute (SBP) and concluded that the addition of dietary sugar may actually help fight melanoma by boosting the number of immune cells.
“Our findings offer new, unprecedented detail into the sugar’s role in cancer,” Ze’ev Ronai, Ph.D., who is the senior author and Scientific Director of SBP’s La Jolla campus, said in a news release. “We found that by tampering with L-fucose metabolism, we could inhibit melanoma tumor metastasis. Not only were the tumors affected but also their microenvironment — the cells surrounding the tumor that play a critical role in sustaining the cancer — making the discovery even more impactful.”
It is known among the scientific community that sugars like glucose and sucrose come from different sources and are used by our bodies in specific ways. Sugars such as L-fucose provide important tags on proteins’ cell-surface that signal inflammation and direct cell migration. Previous research had showed that the variation of L-fucose levels on cells is connected to breast and stomach cancers.
Researchers started by investigating the activating transcription factor 2 (ATF2), a protein that has the potential to control the expression of other proteins and that has been linked to the development of melanoma and other forms of cancer. Ronai’s team is familiar with ATF2 as they have been studying it for over two decades. “To our surprise, one of the genes found to be regulated by ATF2 was fucokinase (FUK), which controls the ability of cells to process the dietary sugar, L-fucose, into a form that is useable for the modification (fucosylation) of proteins, many of which are on the cell surface,” explained Ronai. “In human samples, we found reduced fucosylation in metastatic melanomas and a better prognosis for primary melanomas with increased fucosylation. We suspect that the absence of L-fucose on melanoma cells makes them less sticky and more mobile in the body, making them more likely to metastasize.”
The researchers were able to increase fucosylation in mice models of melanoma, by adding the sugar to their drinking water and by genetic manipulation, with both methods blocking metastasis and tumor growth. “Many patients develop resistance to current melanoma drugs. If we can add something like L-fucose to enhance these therapies, that’s very exciting, and it’s something we’re actively looking into,” noted Eric Lau, Ph.D., who is also a lead author and is now interested in continuing his research on the role of L-fucose in melanoma at the H. Lee Moffitt Cancer Center in Tampa, Florida.
“The dietary result was especially gratifying, because it suggests that modifying fucosylation could be achieved by the simple addition of L-fucose to drinking water,” concluded Ronai. “Our results further suggest that the addition of dietary sugar may help fight melanoma by boosting numbers of helpful immune cells. We are continuing our exploration of how fucosylation and other sugar coatings affect the immune system and impact cancer.”
