A scientific breakthrough at the IRCM could help understand certain cancers

Researchers discover an important protein's mechanism of action

2011-06-14

(Press-News.org) Montréal, June 13, 2011 – A scientific breakthrough by researchers at the Institut de recherches cliniques de Montréal (IRCM) will be published tomorrow in Developmental Cell, a scientific journal of the Cell Press group. Led by Dr. Frédéric Charron, the team of scientists discovered a new requirement for the proper functioning of the Sonic Hedgehog protein.

Sonic Hedgehog belongs to a family of proteins that gives cells the information needed for the embryo to develop properly. It plays a critical role in the development of many of the body's organs, such as the central nervous system. Malfunctions of these proteins are associated with many diseases including cancer, which is the leading cause of death in Canada.

"On one hand, certain molecules travel through our organs (in this case, Sonic Hedgehog) and transmit signals to cells with information on how they should function," explains Luisa Izzi, postdoctoral fellow in Dr. Charron's laboratory and co-first author of the article. "On the other hand, our cells have receptors to receive these signals. The receptors then instruct the cell's DNA as to which genes to turn on or off in order to perform its function."

The team studied the interactions between the Sonic Hedgehog molecule and the recently-identified receptors Boc, Cdon and Gas1, all found on the surface of cells. "Our research showed, unexpectedly, that these receptors are essential for the transmission of the hedgehog molecule's signal," adds Martin Lévesque, an alumnus from Dr. Charron's research unit and co-first author of the article.

"Disrupting the transmission of the Sonic Hedgehog signal can lead to diseases," says Dr. Charron, Director of the IRCM's Molecular Biology of Neural Development research unit. "A better knowledge of the receptors Boc, Cdon and Gas1 might in turn help our understanding of pathologies associated with defective Sonic Hedgehog signalling. Our results could also lead to new avenues for the treatment of certain diseases such as cancer."

### According to the Canadian Cancer Society, an estimated 251,900 new cases of cancer and 75,000 deaths caused by the disease will occur in Canada in 2011. In 2007, cancer surpassed cardiovascular disease as the leading cause of death in Canada.

Research carried out in Dr. Charron's laboratory was funded by the Canadian Cancer Society, the Fonds de recherche en santé du Québec (FRSQ), and the Canadian Institutes of Health Research (CIHR).

For more information, please refer to the article summary published in Developmental Cell: http://www.cell.com/developmental-cell/abstract/S1534-5807(11)00171-7.

In addition to directing this research project, Dr. Charron and his team participated in a second study led by Dr. Benjamin L. Allen from the University of Michigan Medical School. This second study, also to be published in the June 14th issue of Developmental Cell, examined the role of the same receptors (Boc, Cdon and Gas1) in a different system and confirmed the results found at the IRCM. Including these two studies, Dr. Charron's team have published three new discoveries in the past two weeks in Developmental Cell and Neuron.

About Dr. Frédéric Charron Frédéric Charron obtained his PhD in experimental medicine from McGill University. He is an Associate IRCM Research Professor and Director of the Molecular Biology of Neural Development research unit. Dr. Charron is also Associate Research Professor in the Department of Medicine at the Université de Montréal, and associate member of the Department of Medicine (Division of Experimental Medicine), the Department of Biology, and the Department of Anatomy and Cell Biology at McGill University. In addition, he is a member of the McGill Integrated Program in Neuroscience, the Montreal Regional Brain Tumor Research Group at the Montreal Neurological Institute, and the Centre of Excellence in Neurosciences (CENUM) at the Université de Montréal. Dr. Charron is a Research Scholar from the Fonds de recherche en santé du Québec (FRSQ).

About the Institut de recherches cliniques de Montréal (IRCM) Founded in 1967, the IRCM (www.ircm.qc.ca) is currently comprised of 36 research units in various fields, namely immunity and viral infections, cardiovascular and metabolic diseases, cancer, neurobiology and development, systems biology and medicinal chemistry. It also houses three specialized research clinics, seven core facilities and two research platforms with state-of-the-art equipment. The IRCM employs 425 people and is an independent institution affiliated with the Université de Montréal. The IRCM clinic is associated to the Centre hospitalier de l'Université de Montréal (CHUM). The IRCM also maintains a long-standing association with McGill University.

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