Suppression of progranulin expression inhibits bladder cancer growth and sensitizes cancer cells to cisplatin
| Autor: | Andrea Morrione, Igor Moskalev, Ruth Birbe, Alaide Morcavallo, Ryuta Tanimoto, Shi Qiong Xu, Leonard G. Gomella, Marco Genua, Renato V. Iozzo, Antonino Belfiore, Peter C. Black, Simone Buraschi, Stephen C. Peiper, Manuela Stefanello |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Pathology Nude Transgenic Small hairpin RNA Mice Progranulins Cell Movement RNA Small Interfering Tumor anchorage-independent growth 3. Good health Gene Expression Regulation Neoplastic Phenotype motility Oncology bladder cancer Intercellular Signaling Peptides and Proteins Female Research Paper medicine.drug medicine.medical_specialty Cell Survival MAP Kinase Signaling System Mice Nude Motility Mice Transgenic Antineoplastic Agents Small Interfering Cell Line 03 medical and health sciences Downregulation and upregulation Cell Line Tumor tumor formation in vivo mental disorders Biomarkers Tumor progranulin medicine Animals Humans Neoplasm Invasiveness Urothelium Cell Proliferation Cisplatin Neoplastic Bladder cancer Cell growth business.industry medicine.disease Actins 030104 developmental biology Urinary Bladder Neoplasms Gene Expression Regulation Cancer cell Cancer research RNA Neoplasm Transplantation business Biomarkers |
| Zdroj: | Scopus-Elsevier Oncotarget |
| ISSN: | 1949-2553 |
| Popis: | We have recently demonstrated a critical role for progranulin in bladder cancer. Progranulin contributes, as an autocrine growth factor, to the transformed phenotype by modulating Akt-and MAPK-driven motility, invasion and anchorage-independent growth. Progranulin also induces F-actin remodeling by interacting with the F-actin binding protein drebrin. In addition, progranulin is overexpressed in invasive bladder cancer compared to normal tissue controls, suggesting that progranulin might play a key role in driving the transition to the invasive phenotype of urothelial cancer. However, it is not established whether targeting progranulin could have therapeutic effects on bladder cancer. In this study, we stably depleted urothelial cancer cells of endogenous progranulin by shRNA approaches and determined that progranulin depletion severely inhibited the ability of tumorigenic urothelial cancer cells to migrate, invade and grow in anchorage-independency. We further demonstrate that progranulin expression is critical for tumor growth in vivo, in both xenograft and orthotopic tumor models. Notably, progranulin levels correlated with response to cisplatin treatment and were upregulated in bladder tumors. Our data indicate that progranulin may constitute a novel target for therapeutic intervention in bladder tumors. In addition, progranulin may serve as a novel biomarker for bladder cancer. |
| Databáze: | OpenAIRE |
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