EphA2 Identified As Elusive Functional Signaling Receptor for Progranulin; Finding May Aid Advances in Cancer & Neurodegenerative Disease Studies

Progranulin is produced and secreted by most cells in the body. From skin to immune cells, brain to bone marrow cells, progranulin plays a key role in maintaining normal cellular function. In cancer, too much progranulin makes tumors (particularly prostate carcinomas) more aggressive and metastatic, whereas, in neurodegenerative diseases, too little progranulin is associated with disease onset and progression. Until now, studying progranulin has been tricky as the progranulin receptor that communicates biological information to the cell's signaling machinery has remained elusive for decades. Now, researchers at Thomas Jefferson University's Sidney Kimmel Cancer Center have discovered a cell-surface receptor highly expressed by cancerous and brain cells that directly and tightly binds progranulin. Importantly, the researchers also showed that this binding activates a cellular program that makes cancer cells more aggressive. The results were published online on November 30, 2016 in The Journal of Cell Biology. The article is titled “EphA2 Is a Functional Receptor for the Growth Factor Progranulin." "Identifying the functional signaling receptor for progranulin will help us understand how this molecule functions in cancer and whether pharmacologically targeting it will slow the progression of a number of cancers," says Renato V. Iozzo, M.D., Ph.D., Gonzalo E. Aponte Professor and Deputy Chair of the Department of Pathology, Anatomy & Cell Biology at Thomas Jefferson University and researcher at the Sidney Kimmel Cancer Center at Jefferson.
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