It has long been known that our bodies derive energy from sugar. Researchers at RPTU University Kaiserslautern-Landau have now discovered that sugar breakdown produces an intermediate product that is also crucial for the motility of human cells. The new findings are likely to be relevant for understanding several biological processes, including cell migration in embryonic development, the migration of metastatic cancer cells and wound healing.
Our bodies consist of an estimated 32 trillion individual cells. For these cells to form a coherent organism, most of them must be firmly anchored in their environment. To achieve this, cells use, among other structures, so-called focal adhesions. These anchorage points consist of protein accumulations that bind, on the one hand, to molecules surrounding the cells and, on the other hand, to the cell's skeleton, the so-called cytoskeleton. When a cell moves, for example during wound healing or to reach its destination during embryonic development, both the cytoskeleton and the focal adhesions must be dynamically assembled and disassembled. If this occurs “out of turn,” it can result in the spread of tumor cells.
Exactly what controls the remodeling of the cytoskeleton and adhesions is still far from clear. This is precisely where a recent study by researchers at RPTU comes in: In a collaboration with the Screening and Cellular Imaging Unit of the Leibniz Forschungsinstitut für Molekulare Pharmakologie, a team led by Professor Tanja Maritzen used small RNA molecules, known as siRNAs, to suppress the production of individual proteins – and then observed in each case how this affected the cells: “To do this, we stained the adhesion structures of the cells, examined them under a microscope, and then used automatic image analysis to evaluate whether their size or number had changed,” reports Maritzen, who heads the Nanophysiology working group at the RPTU's Department of Biology.
In this manner, the research team examined a total of 18,000 different proteins found in our bodies – and came across the metabolic enzyme aldolase A, in the absence of which the cells were larger and displayed more focal adhesions. Strikingly, a special sugar accumulated in the aldolase-depleted cells – which in turn formed a bond with a specific protein. Put simply, this bond triggers the cells to become motile.
Lennart Hoffmann, first author of the study, explains: "We have discovered that one of the small compounds produced during sugar metabolism, a molecule with the complicated name fructose 1,6-bisphosphate, or FBP for short, is not only an intermediate product in the production of energy from sugar, but also a signal for the remodeling of cytoskeleton and adhesions." More specifically, FBP ensures that an activator of cytoskeletal remodeling, a protein called Rac1, is no longer inactive. "Active Rac1 then leads to the generation of new cytoskeletal elements at the cell front, which causes the cell membrane to move forward – with simultaneous anchoring via new adhesion points."
It has long been suspected that cellular energy metabolism influences cytoskeletal remodeling and the formation of adhesion structures: “Just as a runner shouldn’t start a race in a malnourished state, it makes sense that a cell receives feedback on its energy status before it embarks on the energy-intensive remodeling of its cytoskeleton,” concludes Tanja Maritzen.
The new findings are significant for several aspects of biology: “In the narrower sense, for the areas that deal with cell adhesion and migration. Both the migration of immune cells and metastatic cancer cells could be influenced by the mechanism we have discovered,” explains Tanja Maritzen, also with a view to potential follow-up studies. However, the cytoskeleton also plays a role in other processes such as the formation of new blood vessels or insulin secretion, so the results are equally relevant for researchers working on these processes.
Prof. Dr. Tanja Maritzen
RPTU University Kaiserslautern-Landau
E-Mail: maritzen[@]rptu.de
Hoffmann, L., Duchmann, M., Lazarow, K., Huang, Y.H., Lukas, F., Lo, W.T., Feil, R., Schmied, C., Lehmann, M., Lunn, J.E., Piazza, I., von Kries, J.P., Haucke, V., Maritzen, T. (2026) Fructose-1,6-bisphosphate couples glycolytic activity to cell adhesion. Nature Cell Biology. DOI: 10.1038/s41556-026-01911
https://www.nature.com/articles/s41556-026-01911-1
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Biology, Medicine, Nutrition / healthcare / nursing
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