A novel role for drebrin in regulating progranulin bioactivity in bladder cancer.

Authors

Shi-Qiong Xu, Endocrine Mechanisms and Hormone Action Program, Department of Urology, Kimmel Cancer Center, Thomas Jefferson UniversityFollow
Simone Buraschi, Cancer Cell Biology and Signaling Program, Department of Pathology, Anatomy and Cell Biology, Kimmel Cancer Center, Thomas Jefferson UniversityFollow
Alaide Morcavallo, Department of Urology and Biology of Prostate Cancer Program, Thomas Jefferson University; Department of Health and Endocrinology, University Magna Graecia of CatanzaroFollow
Marco Genua, Department of Urology and Biology of Prostate Cancer Program, Thomas Jefferson UniversityFollow
Tomoaki Shirao, Department of Neurobiology and Behavior, Gunma University School of Medicine
Stephen C Peiper, Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, Philadelphia, Pennsylvania, United States of AmericaFollow
Leonard G Gomella, Department of Urology and Biology of Prostate Cancer Program, Thomas Jefferson UniversityFollow
Ruth Birbe, Department of Pathology, Anatomy and Cell Biology, Kimmel Cancer Center, Thomas Jefferson UniversityFollow
Antonino Belfiore, Department of Health and Endocrinology, University Magna Graecia of CatanzaroFollow
Renato V Iozzo, Department of Pathology, Anatomy and Cell Biology, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PennsylvaniaFollow
Andrea Morrione, Department of Urology, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PennsylvaniaFollow

Document Type

Article

Publication Date

5-10-2015

Comments

This article has been peer reviewed. It was published in: Oncotarget.

Volume 6, Issue 13, 2015, Pages 10825-10839.

The published version is available at http://www.impactjournals.com/oncotarget/index.php?journal=oncotarget&page=article&op=view&path[]=3424

Copyright © 2015 The Authors

Abstract

We recently established a critical role for the growth factor progranulin in bladder cancer insofar as progranulin promotes urothelial cancer cell motility and contributes, as an autocrine growth factor, to the transformed phenotype by modulating invasion and anchorage-independent growth. In addition, progranulin expression is upregulated in invasive bladder cancer tissues compared to normal controls. However, the molecular mechanisms of progranulin action in bladder cancer have not been fully elucidated. In this study, we searched for novel progranulin-interacting proteins using pull-down assays with recombinant progranulin and proteomics. We discovered that drebrin, an F-actin binding protein, bound progranulin in urothelial cancer cells. We characterized drebrin function in urothelial cancer cell lines and showed that drebrin is critical for progranulin-dependent activation of the Akt and MAPK pathways and modulates motility, invasion and anchorage-independent growth. In addition, drebrin regulates tumor formation in vivo and its expression is upregulated in bladder cancer tissues compared to normal tissue controls. Our data are translationally relevant as indicate that drebrin exerts an essential functional role in the regulation of progranulin action and may constitute a novel target for therapeutic intervention in bladder tumors. In addition, drebrin may serve as novel biomarker for bladder cancer.

Recommended Citation

Xu, Shi-Qiong; Buraschi, Simone; Morcavallo, Alaide; Genua, Marco; Shirao, Tomoaki; Peiper, Stephen C; Gomella, Leonard G; Birbe, Ruth; Belfiore, Antonino; Iozzo, Renato V; and Morrione, Andrea, "A novel role for drebrin in regulating progranulin bioactivity in bladder cancer." (2015). Department of Urology Faculty Papers. Paper 27.
https://jdc.jefferson.edu/urologyfp/27

PubMed ID

25839164