Quantitative Proteomics of Urinary Bladder Cancer Cell Lines Identify UAP1 as a Potential Therapeutic Target.

Vinuth N Puttamallesh,Prashant Kumar,Akhilesh Pandey,Aditi Chatterjee,Harsha Gowda,Bipin Nair,Ankit Jain,Kirti Gondkar,Barnali Deb

doi:10.3390/genes11070763

Abstract

Bladder carcinoma (BC) incidence and mortality rates are increasing worldwide. The development of novel therapeutic strategies is required to improve clinical management of this cancer. Aberrant protein expression may lead to cancer initiation and progression. Therefore, the identification of these potential protein targets and limiting their expression levels would provide alternative treatment options. In this study, we utilized a liquid-chromatography tandem mass spectrometry-based global proteomics approach to identify differentially expressed proteins in bladder cancer cell lines. A total of 3913 proteins were identified in this study, of which 479 proteins were overexpressed and 141 proteins were downregulated in 4 out of 6 BC cell lines when compared with normal human urothelial cell line (TERT-NHUC). We evaluated the role of UDP-N-acetylhexosamine pyrophosphorylase (UAP1) in bladder cancer pathogenesis. The silencing of UAP1 led to reduction in proliferation, invasion, colony formation and migration capability of bladder cancer cell lines. Thus, our study reveals UAP1 as a promising therapeutic target for bladder cancer.

Highlights

Bladder carcinoma (BC) is the most common malignancy of the urinary tract
We identified and quantified 3913 proteins across all the cell lines in triplicate mass spectrometry analysis and calculated their fold-change values based on reporter ion intensities (Supplementary Table S1; Supplementary Figure S1)
Our results show the importance of UAP1 in the colony formation of BC cells

Summary

Introduction

Bladder carcinoma (BC) is the most common malignancy of the urinary tract. Majority of the patients are diagnosed as non-muscle invasive (NMIBC; 60%) with a recurrence rate of 50%–70%and about 20% of patients are diagnosed as muscle invasive bladder cancer (MIBC) [1]. Bladder carcinoma (BC) is the most common malignancy of the urinary tract. Majority of the patients are diagnosed as non-muscle invasive (NMIBC; 60%) with a recurrence rate of 50%–70%. About 20% of patients are diagnosed as muscle invasive bladder cancer (MIBC) [1]. The risk of progression for NMIBC to MIBC after 5 years ranges from 6% to 45% [2,3]. MIBCs are biologically aggressive, with less than 15% five-year survival rate [4]. In the past few years, the surgical advancements have improved the outcomes of the patients. Despite the use of neoadjuvant and adjuvant therapies, the long term survival rates in BC patients has remained unchanged for over a decade [5]

Methods

Results

Conclusion