Signalling the End of Cancer

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Researchers identify signalling pathway in normal tissue that protects against brain cancer.
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Dr. Wallace (pictured), Krembil Senior Scientist and Co-Director of the Donald K. Johnson Eye Institute, and collaborators published these findings in the journal eLife.
Medulloblastoma is the most common type of brain tumour that can develop in children. The disease develops when normal cells undergo progressive genetic changes that enable them to multiply uncontrollably.

Much of the research on cancer progression focuses on defining these genetic changes; however, another key to understanding how cancer forms is the role of surrounding tissues– the ‘tumour microenvironment’—in preventing or supporting tumour growth.

Krembil Senior Scientist Dr. Valerie Wallace, along with collaborators at the Ottawa Health Research Institute and the Hospital for Sick Children, published a study where they explored how the tumour microenvironment controls medulloblastoma development.

Using an experimental model, Dr. Wallace’s team discovered that certain proteins found in the surrounding tissues that control the Norrin/Frizzled4 signalling pathway—a coordinated set of molecular signals that govern tissue structure and blood vessel development—can stop cancer progression early on. Blocking the Norrin/Frizzled4 signal enabled pre-cancerous growths to form and accelerated tumour initiation. The results suggest that, when functioning normally, the Norrin/Frizzled4 pathway may help prevent cancer progression.

“By identifying a potential role for these proteins in medulloblastoma development, our research reveals new observations that down the road might change what happens in the clinic,” says Dr. Wallace.  “Our next step will be to investigate what it is exactly about dysfunctional Norrin/Frizzled4 signalling that makes cells more likely to become cancerous, so we can devise strategies to prevent tumour growth.”

This work was supported by the Canadian Cancer Society, the Cancer Research Society and the Toronto General & Western Hospital Foundation.​

Bassett EA, Tokarew N, Allemano EA, Mazerolle C, Morin K, Mears AJ, McNeill B, Ringuette R, Campbell C, Smiley S, Pokrajac NT, Dubuc AM, Ramaswamy V, Northcott PA, Remke M, Monnier PP, Potter D, Paes K, Kirkpatrick LL, Coker KJ, Rice DS,Perez-Iratxeta C, Taylor MD, Wallace VA. Norrin/Frizzled4 signalling in the preneoplastic niche blocks medulloblastoma initiation. Elife. 2016 Nov 8. PMID: 27823583.