Suppression of progranulin expression inhibits bladder cancer growth and sensitizes cancer cells to cisplatin

Simone Buraschi, Shi Qiong Xu, Manuela Stefanello, Igor Moskalev, Alaide Morcavallo, Marco Genua, Ryuta Tanimoto, Ruth Birbe, Stephen C. Peiper, Leonard G. Gomella, Antonino Belfiore, Peter C. Black, Renato V. Iozzo, Andrea Morrione

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)39980-39995
Number of pages16
JournalOncotarget
Volume7
Issue number26
Publication statusPublished - 2016
Externally publishedYes

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Keywords

  • Anchorage-independent growth
  • Bladder cancer
  • Motility
  • Progranulin
  • Tumor formation in vivo

ASJC Scopus subject areas

  • Oncology

Cite this

Buraschi, S., Xu, S. Q., Stefanello, M., Moskalev, I., Morcavallo, A., Genua, M., Tanimoto, R., Birbe, R., Peiper, S. C., Gomella, L. G., Belfiore, A., Black, P. C., Iozzo, R. V., & Morrione, A. (2016). Suppression of progranulin expression inhibits bladder cancer growth and sensitizes cancer cells to cisplatin. Oncotarget, 7(26), 39980-39995.