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Kirill Rosen

Title:
Associate professor
Institute:
Dalhousie University, Halifax
Department:
Pediatrics, Biochemistry & Molecular Biology
Province:
Nova Scotia
Research Projects
Project title:
Beta-catenin as a mediator of three-dimensional tumor growth
Funding period:
2010-2012
Program:
Operating Grant (Basic Research)
Summary:
The cells lining various human organs (epithelial cells) form a single layer. Cells that detach from this layer die. Many cancers are derived from epithelial cells. In order to spread throughout the body epithelial cells that have become cancerous have to survive outside of the epithelial layer. Genetic alterations in cancer cells often activate a protein called beta-catenin, and this is thought to contribute to the progression of many cancers. We found that beta-catenin rescues malignant cells that have detached from the original epithelial layer from demise by reducing levels of a cell death-inducing protein called Death-Associated Protein Kinase-2 (DAPk-2) in these cells. Others have established that cell survival is directly controlled by a specialized machinery that consists of many proteins, but the mechanisms linking DAPk-2 with this machinery are presently not known. Our goal is to understand how beta-catenin-driven reduction of cellular DAPk-2 levels prevents the indicated machinery from killing detached cancer cells. We further plan to investigate whether this reduction is required for the spread of malignant cells throughout the body. If successful, our work could lead to a new type of cancer therapy based on blocking the ability of cancer cells to grow outside of their original location.
Past CRS projects:
2007 Death-Associated Protein Kinase-2 as a suppressor of beta-catenin-dependent malignant transformation of epithelial cells









