A research team based in Winnipeg, Canada is using the Canadian Light Source (CLS), a national research facility of the University of Saskatchewan to find new, cutting-edge ways to battle cancer.

Jörg Stetefeld, Ph.D., a professor of biochemistry and Tier-1 Canada Research Chair in Structural Biology and Biophysics at the University of Manitoba, is leading groundbreaking research into how netrin-1 (Ntn-1) — a multifunctional neuronal signaling molecule related to cell migration and differentiation —  creates filaments and binds to receptors in cells.

Because netrin-1 is considered the key player for the migration of cancer cells, Stetefeld said this research could help in the development of novel cancer treatments.

“If we can understand how netrin binds these receptors, we’re sitting in the driver’s seat to develop approaches to block this interaction,” Stetefeld explained.

“Why do we want to block netrin-1? In simple terms, because if you block this interaction, we kill the cancer cell.”

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Early research
Earlier research published in 2016 led to the development of new antibody treatments in Europe for combating breast cancer, said Stetefeld. He hopes this new research, which was published in the journal Nature, can lead to better drugs and treatments as well.

“The work we publish now with the help of the synchrotron, where we measured the key data, is to develop drugs against netrin, specifically when it forms this kind of filament,” Stetefeld said. “Now we really want to develop applications for structure-based drug design.” [1]

By using one of the beamlines at the CLS designed for crystallography, the researchers examined how the netrin-1 forms binding filaments with “close to atomic-resolution data.” The next step is to determine how to prevent netrin from forming filaments, giving them what Stetefeld calls “the perfect point of attack” to cause death in cancer cells.

In their study, Stetefeld and his team presented a molecular understanding of netrin-1 mediated interactions with glycosaminoglycan chains of diverse heparan sulfate proteoglycans (HSPGs) and short heparin oligosaccharides.

While there is still much investigation to be done, Stetefeld is excited to continue this research with the help of the technology at the CLS in the hope of finding a breakthrough in the battle against cancer.

“There’s this naive or romantic view that ‘eventually, my work will contribute to beating cancer.’ I have a great team, including students. To work with young people is a gift. To see how they burn for it, it’s a huge motivation.”

[1] Meier M, Gupta M, Akgül S, McDougall M, Imhof T, Nikodemus D, Reuten R, Moya-Torres A, To V, Ferens F, Heide F, Padilla-Meier GP, Kukura P, Huang W, Gerisch B, Mörgelin M, Poole K, Antebi A, Koch M, Stetefeld J. The dynamic nature of netrin-1 and the structural basis for glycosaminoglycan fragment-induced filament formation. Nat Commun. 2023 Mar 3;14(1):1226. doi: 10.1038/s41467-023-36692-w. PMID: 36869049; PMCID: PMC9984387.[Article]

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