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Cancer Center Leader’s Discovery in Cell Signaling Featured on Cover of Science 

Work by Carol Williams, PhD, may lead to therapies that prevent the promotion and spread of cancer cells


Cover Image: This week features a Research Article that describes how inhibition of adenosine receptors could reduce metastasis by enhancing prenylation-dependent signaling that promotes cell-cell adhesion.  The image shows cells that are scattering after exposure to an adenosine receptor agonist (upper group) and cells that remain in contact because they have not been exposed to the agonist (lower group).

MCW cancer researcher Carol L. Williams, PhD, and her research team have identified a way to block receptors that might be responsible for signaling lung, breast, and pancreatic cancer metastasis.  This work, including a cover picture of cancer cells moving away from each other when the receptors are active, was published in the May 28th issue of Science Signaling.  

Dr. Williams recently presented this work to Cancer Center leadership and Joseph E. Kerschner, MD, Dean of the Medical School and Executive Vice President. Ming You, MD, PhD, Director of the Cancer Center and Joseph F. Heil, Jr., Chair in Molecular Oncogenesis, stated, “We’re very excited about this work, which may lead to new strategies to stop these receptors from promoting cancer.”   

This study was conducted by multiple members of Dr. Williams’ laboratory, including Dr. Elizabeth Ntantie, who is lead author of the report, as well as several MCW collaborating investigators, including Drs. John Auchampach, Balaraman Kalyanaraman and Michael Dwinell. 

Dr. Williams’ research team found that adenosine (which is made by tumor cells) can activate receptors on the surface of the tumor cells, causing the cells to move away from each other in a process called cell scattering.  The research team found that cells scatter when adenosine alters the interaction of two proteins called Rap1B and SmgGDS in a novel biochemical process that the investigators discovered while conducting the study.  The scattering of the tumor cells helps them disperse throughout the body, resulting in metastasis.

“Our findings indicate that adenosine and its receptors might promote cancer metastasis by altering proteins such as Rap1B and SmgGDS in a way that no one had previously suspected,” said Dr. Williams. “The results of our study lead to the exciting possibility that drugs that block these actions of adenosine might diminish metastasis.” 

Moving forward, Dr. Williams and her team are developing a therapeutic strategy that will stop adenosine and its receptors from signaling on the cellular level, as a novel approach to prevent cancer development and metastasis.

Dr. Williams is the co-leader of the Cancer Cell Signaling and Metabolism program at the MCW Cancer Center.  She is Professor of Pharmacology and Toxicology, and a member of the Cancer Center and Cardiovascular Center.  Her research focuses on signaling by members of the Ras and Rho families of small GTPases in several types of cancer, including lung and breast cancer, with the aim of developing novel ways to therapeutically manipulate the functions of small GTPases in cancer.

Authors of the manuscript are Elizabeth Ntantie, PhD, former doctoral student and Research Assistant in Pharmacology and Toxicology; Patrick Gonyo, Research Assistant in Pharmacology and Toxicology; Ellen Lorimer, Research Associate in Pharmacology and Toxicology; Andrew Hauser, PhD, former doctoral student and Research Assistant in Pharmacology and Toxicology; Nathan Schuld, Research Assistant in Pharmacology and Toxicology; Donna McAllister, Research Associate in Biophysics; Balaraman Kalyanaraman, PhD, Harry R. & Angeline E. Quadracci Professor in Parkinson’s Research and Chairman of Biophysics; Michael Dwinell, PhD, Associate Professor of Microbiology and Molecular Genetics; John Auchampach, PhD, Professor of Pharmacology and Toxicology; and Carol Williams, PhD, Professor of Pharmacology and Toxicology.

Read the full article in Science Signaling (link to: http://stke.sciencemag.org/cgi/content/full/sigtrans;6/277/ra39)

Science Signaling is a publication of the American Association for the Advancement of Science. 

 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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