Targeting Receptor EphA2 Reduces Bladder Cancer Tumor Growth and Increases Chemotherapy Effectiveness

An international team of investigators has recently discovered that the receptor tyrosine-kinase EphA2 activated by the growth factor progranulin is a tumorigenic driver of bladder cancer progression.

The study, “Progranulin/EphA2 axis: A novel oncogenic mechanism in bladder cancer,” has been recently published in the international-peer-reviewed journal Matrix Biology. The paper describes how EphA2 depletion severely blunted progranulin-dependent motility and anchorage-independent growth, and sensitized bladder cancer cells to cisplatin treatment.

The authors, including Dr. Andrea Morrione, currently at the Sbarro Institute for Cancer Research and Molecular Medicine, and the Center for Biotechnology at Temple University, Dr. Renato V. Iozzo from the Department of Pathology, Anatomy and Cell Biology at Thomas Jefferson University, and Dr. Antonino Belfiore from the University of Catania, Italy, had previously demonstrated that the growth factor progranulin plays a critical role in bladder cancer by modulating tumor cell motility and invasion, and discovered that progranulin targeting markedly reduces in vivo tumor growth and sensitizes urothelial cancer cells to cisplatin treatment. The authors recently identified EphA2, a member of a large family of receptor tyrosine-kinases, as the functional receptor for progranulin. However, It was not previously established whether EphA2 plays an oncogenic role in bladder cancer.

This study demonstrates that progranulin is the predominant EphA2 ligand in bladder cancer. Progranulin evokes Akt- and Erk1/2-mediated EphA2 phosphorylation at Ser897, which could drive bladder tumorigenesis. They further defined the mechanisms of progranulin/EphA2-dependent motility by identifying liprin-α1 as a novel progranulin-dependent EphA2 interacting protein and establishing its critical role in cell motility.

As stated by Dr. Antonio Giordano, Founder and Director of the Sbarro Health Research Organization at Temple University, “the discovery of EphA2 as the functional signaling receptor for progranulin and the identification of novel downstream effectors offers a new avenue for understanding the underlying mechanism of progranulin action, and may constitute novel clinical and therapeutic targets in bladder cancer.”

Bladder cancer is one of the most common and aggressive cancers worldwide and, regardless of the treatment, often recurs and spreads to surrounding tissues. Thus, a deeper knowledge of the mechanisms driving bladder tumorigenesis is critical for novel rational therapeutic strategies.

About the Sbarro Health Research Organization
The Sbarro Health Research Organization (SHRO) is non-profit charity committed to funding excellence in basic genetic research to cure and diagnose cancer, cardiovascular diseases, diabetes and other chronic illnesses and to foster the training of young doctors in a spirit of professionalism and humanism. To learn more about the SHRO please visit www.shro.org

Original Newswise Release        PubMed Abstract     Matrix Biology Article