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Understanding the checks and balances that govern when and how much cells grow is key to understanding cancer. A study published in November 2013 by the Gingras lab uncovers pieces of the complex mosaic of molecular interactions or signals that govern the normal growth of cells, tissue, and organs.

Within all animal cells an important series of switches causes them to stop growing once a tissue has attained the right size. “This system is called the Hippo pathway because deregulation of this system leads to overgrowth, a ‘hippopotamus’ phenotype. The Hippo pathway consists of proteins that interact with one another, sense other control systems within our cells, and send signals to stop the cell growth,” says Dr. Gingras.

“Our study identified 749 interactions between proteins and enzymes that play a role in telling a cell when to stop growing. Of these, 600 have not been previously recognized in the Hippo pathway,” she says.

“These findings are promising because, to date, there are no drugs directed at the components of the Hippo pathway,” adds Dr. Jim Woodgett, Director of the Lunenfeld-Tanenbaum Research Institute. “Anne-Claude’s team’s work has added many new candidates for therapeutic intervention that may, for example, help in restricting the uncontrolled growth of tumour cells.”

Dr. Amber Couzens
Dr.Amber Couzens

Lead author Dr. Amber Couzens is extending the findings by defining the discrete mechanisms that govern these interactions. Since completing her PhD at York University in 2011, her goal has been to continue to study cell signaling with a systems biology approach. “The facilities and support from Dr. Gingras and colleagues here at the institute really helped make this study possible and will be a great resource for other researchers in the Hippo field going forward,” she adds.

Dr. Gingras is a Senior Investigator at Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, and Associate Professor of Molecular Genetics at University of Toronto. Other co-authors include several from Lunenfeld-Tanenbaum Research Institute: James Dr. R. Knight, Michelle J. Kean, Alexander Weiss, Wade H. Dunham, Zhen-Yuan Lin, Richard D. Bagshaw, Frank Sicheri, the late Tony Pawson, and Jeffrey L. Wrana. Other co-authors are from National University of Singapore. The study was funded by Canadian Institutes of Health Research and the Government of Ontario.

The research was performed in human cells and was published November 19, 2013 in Science Signaling. The paper is titled “Protein Interaction Network of the Mammalian Hippo Pathway Reveals Mechanisms of Kinase-Phosphatase Interactions.



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