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.

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