Progranulin and EGFR modulate receptor-like tyrosine kinase sorting and stability in mesothelioma cells

Author:

Ventura Elisa1,Belfiore Antonino2,Iozzo Renato V.3ORCID,Giordano Antonio14,Morrione Andrea1ORCID

Affiliation:

1. Sbarro Institute for Cancer Research and Molecular Medicine, Center for Biotechnology, Department of Biology, College of Science and Technology, Temple University, Philadelphia, Pennsylvania, United States

2. Department of Clinical and Experimental Medicine, Endocrinology Unit, University of Catania, Garibaldi-Nesima Hospital, Catania, Italy

3. Department of Pathology and Genomic Medicine, and the Translational Cellular Oncology Program, Sidney Kimmel Cancer Center, Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia, Pennsylvania, United States

4. Department of Biomedical Biotechnologies, University of Siena, Siena, Italy

Abstract

The growth factor progranulin has pro-tumorigenic activity. In mesothelioma, progranulin signaling is mediated by EGFR and RYK, a co-receptor of the Wnt signaling. However, the molecular mechanisms regulating progranulin action are not well defined. Here, we demonstrated that progranulin binds RYK and regulates its ubiquitination, internalization, and trafficking. We also uncovered a role for EGFR in modulating RYK stability. Overall, these results highlight a complex modulation of RYK activity by progranulin and EGFR in mesothelioma.

Funder

HHS | NIH | National Cancer Institute

Sbarro Health Research Organization

Publisher

American Physiological Society

Subject

Cell Biology,Physiology

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