Proteomics analysis of bladder cancer invasion: targeting EIF3D for therapeutic intervention

Latosinska, A. et al. (2017) Proteomics analysis of bladder cancer invasion: targeting EIF3D for therapeutic intervention. Oncotarget, 8(41), pp. 69435-69455. (doi: 10.18632/oncotarget.17279) (PMID:28488575)

Abstract

Patients with advanced bladder cancer have poor outcomes, indicating a need for more efficient therapeutic approaches. This study characterizes proteomic changes underlying bladder cancer invasion aiming for the better understanding of disease pathophysiology and identification of drug targets. High resolution liquid chromatography coupled to tandem mass spectrometry analysis of tissue specimens from patients with non-muscle invasive (NMIBC, stage pTa) and muscle invasive bladder cancer (MIBC, stages pT2+) was conducted. Comparative analysis identified 144 differentially expressed proteins between analyzed groups. These included proteins previously associated with bladder cancer and also additional novel such as PGRMC1, FUCA1, BROX and PSMD12, which were further confirmed by immunohistochemistry. Pathway and interactome analysis predicted strong activation in muscle invasive bladder cancer of pathways associated with protein synthesis e.g. eIF2 and mTOR signaling. Knock-down of eukaryotic translation initiation factor 3 subunit D (EIF3D) (overexpressed in muscle invasive disease) in metastatic T24M bladder cancer cells inhibited cell proliferation, migration, and colony formation in vitro and decreased tumor growth in xenograft models. By contrast, knocking down GTP-binding protein Rheb (which is upstream of EIF3D) recapitulated the effects of EIF3D knockdown in vitro, but not in vivo. Collectively, this study represents a comprehensive analysis of NMIBC and MIBC providing a resource for future studies. The results highlight EIF3D as a potential therapeutic target.

• Item Type: Articles
• Keywords: EIF3D, RHEB, bladder cancer, tissue proteomics, translation.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Mullen, Dr Bill and Mischak, Professor Harald
• Authors: Latosinska, A., Mokou, M., Makridakis, M., Mullen, W., Zoidakis, J., Lygirou, V., Frantzi, M., Katafigiotis, I., Stravodimos, K., Hupe, M. C., Dobrzynski, M., Kolch, W., Merseburger, A. S., Mischak, H., Roubelakis, M. G., and Vlahou, A.
• College/School: College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
• Journal Name: Oncotarget
• Publisher: Impact Journals
• ISSN: 1949-2553
• ISSN (Online): 1949-2553
• Published Online: 20 April 2017
• Copyright Holders: Copyright © 2017 The Authors
• First Published: First published in Oncotarget 8(41): 69435-69455
• Publisher Policy: Reproduced under a Creative Commons License