Deeper Understanding of Malignant Mesothelioma Reveals New Novel Targets to Investigate

Progranulin is a growth factor in cellular activity that is known to play a key role in the proliferation of tumors. In the case of malignant mesothelioma, researchers are honing in on how progranulin interacts with signal pathways through a system of proteins and receptors in our cells. 

A team of investigators from the Sbarro Institute for Cancer Research and Molecular Medicine, and the Center for Biotechnology at Temple University, including Dr. Elisa Ventura, Dr. Antonio Giordano and Dr. Andrea Morrione, in collaboration with Dr. Renato V. Iozzo from the Department of Pathology, Anatomy and Cell Biology at Department of Pathology & Genomic Medicine at TThomas Jefferson University, and Dr. Antonino Belfiore from the University of Catania, Italy, has previously demonstrated that in mesothelioma, progranulin regulates cell migration, invasion, adhesion, and in vivo tumor formation.

The same team of investigators has recently published their characterization of the molecular mechanisms of progranulin oncogenic action in mesothelioma as relates to the Epidermal Growth Factor Receptor (EGFR) and RYKs. The study entitled “Progranulin and EGFR modulate RYK (Receptor-like Tyrosine Kinase) sorting and stability in mesothelioma cells,” appears in the international-peer-reviewed journal American Journal of Physiology Cell Physiology.

Malignant mesothelioma is a very aggressive cancer with a very poor survival and limited treatment options. Thus, a deeper knowledge of the mechanisms driving mesothelioma initiation and progression is critical for novel therapeutic strategies. In this study, the authors demonstrated that progranulin directly interacts with RYK and functionally modulates its intracellular trafficking in mesothelioma cells, thereby regulating RYK stability and action. They also showed that RYK complexes with the EGFR, which modulates RYK stability in mesothelioma cells, thereby indicating that progranulin-dependent downstream signaling depends on RYK and EGFR internalization and sorting.

“The discovery of RYK and EGFR as the functional signaling receptors for progranulin offers a new avenue for understanding progranulin oncogenic action,” says Giordano, President of the Sbarro Health Research Organization (SHRO) at Temple University, “and the identification of novel proteins involved in regulatory mechanisms may constitute novel therapeutic targets in Malignant Mesothelioma.”

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.