UM Neuroscience Research Team Advances Our Understanding of Childhood Tumors
While neuroblastoma is considered a rare cancer, it is the most common type of solid tumor found in children, accounting for about 50% of all cancers in infants younger than one year of age. Neuroblastoma tumors most often arise from neurons in the adrenal gland of the sympathetic nervous system, which is the network of nerves commonly associated with the body’s “fight or flight” response. How fast the neuroblastoma tumor can grow and spread are key factors in determining the survival rates of patients. Recent work by Neuroscience Professor Mark Grimes, just published in the journal Molecular Biology of the Cell, sheds new light on how neuroblastoma cells may lose control of both their growth rates and their ability to respond to normal developmental cues.
Specific groups of proteins are referred to as oncogenes because they are closely associated with a role in cancer formation. The Grimes lab has been investigating how one of the best known oncogene families, the SRC family kinases (SFKs), are regulated in neuroblastoma cells. His group, which includes both graduate and undergraduate students, found that another protein, PAG1, controls the location and activity of the SFKs. PAG1 is a structural protein that acts to link SFKs with other proteins that usually render the SKFs inactive. Their research shows that when PAG1 is disrupted, and cannot control SFK activity, neuroblastoma cells grow faster and form larger growths. The disruption of PAG1 also prevents these cells from properly responding to the signaling cues that control their further development (differentiation) and growth rate. Thus, by controlling the location of SFKs within the cell, the group discovered that PAG1 regulates SFK activity, and when PAG1 is lost, cells can no longer respond to the signals that regulate their growth and development. In this way, PAG1 appears to be important for both preventing cancers, such as neuroblastoma, and promoting normal neuronal differentiation. It is especially notable that the authors of the publication include Lauren Foltz and Juan Palacios-Moreno, both of whom completed their PhD under the mentorship of Mark Grimes, as well as UM undergraduate neuroscience majors Makenzie Mayfield, Jordan Dillon, and Jed Syrenne.
Lauren Foltz, Ph.D., contributed to this article.
PAG1 directs SRC-family kinase intracellular localization to mediate receptor tyrosine kinase-induced differentiation. Foltz L, Palacios-Moreno J, Mayfield M, Kinch S, Dillon J, Syrenne J, Levy T, Grimes M. Mol Biol Cell. 2020 Jul 29. Online ahead of print. PMID: 32726167
Image above: Neuroblastoma cells
Photo credit: Dr. Katie George