May 25, 2010 (Toronto, ON) A team of Lunenfeld scientists including Drs. Helen McNeill, Tony Pawson, Xaralabos (Bobby) Varelas, and Jeffrey Wrana, as well as colleagues at the University of Toronto, have discovered new ways in which cell proliferation and tissue growth are coordinated, by elucidating the varied functions of a protein called TAZ.
The finding provides researchers with a deeper understanding of the processes involved in cell growth and metastases, and will help open the door to new directions in the treatment of kidney disease, cancer, as well as other human illnesses.
The discovery was reported as the cover story on April 20 in the leading biomedical journal Developmental Cell.
The research team, led by Dr. Liliana Attisano (Department of Biochemistry, University of Toronto), used the Lunenfeld’s leading-edge robotics facility pioneered by Dr. Wrana, to explore a cellular signalling pathway known as ‘Wnt.’ This pathway is involved in cellular processes that determine a cell’s fate (i.e., whether it develops into one cell type or another), and proliferation.
Normal human development requires precisely coordinated cellular events mediated through growth and proliferation ‘signals,’ to ensure appropriate organ architecture and size. When defective or misregulated, these developmental pathways can lead to cancer or other illnesses.
While exploring the Wnt pathway in mouse models, Dr. Attisano and her colleagues at the Lunenfeld discovered that the TAZ protein plays an important role in meditating this pathway. Researchers had previously known that TAZ is regulated by a different control pathway known as ‘Hippo,’ which has been explored in previous studies by Dr. McNeill.
The current discovery has revealed a new role for TAZ and the Hippo pathway in regulating the Wnt pathway, which together work in concert to control tissue growth and thus define organ size.
“We were most surprised and excited to find that the TAZ protein is a key player in coordinating two biological processes: defining both an organ’s size and regulating cellular differentiation,” said Dr. Attisano.
Dr. Attisano explained that, when disrupted, the Wnt pathway can cause cellular changes that may lead to polycystic kidney disease, cancer, and other human illnesses. Understanding more about this pathway will give researchers a better understanding of human diseases, as well as open the door to new targets for treatment.
“Our study shows the significance of the Hippo pathway in coordinating cellular events, and highlights the value of using unbiased screening approaches to uncover novel links between the pathways that control development of our tissues,” said Dr. Varelas, lead author of the study.
The finding has resonated amongst the international biomedical community: editors in leading biomedical journals including Science, as well as Nature Reviews Cancer have highlighted the study and alluded to its importance in understanding key biological processes.