ABSTRACT
BACKGROUND: Urothelial carcinoma (UC) is a major health problem in the general population. We aimed to evaluate the function of Cullin-1 (CUL1) and unravel its underlying molecular mechanism to develop novel treatment options equivalent to UC. METHODS: To evaluate the function of CUL1, a group of 132 pairs of UC patients were recruited for this study. UC tissues and their adjacent noncancerous tissues (NCTs) were collected between 2008 and 2009. We used immunohistochemistry to analyse the correlation between CUL1 expression and clinicopathologic variables and patient survival. RESULTS: CUL1 was dramatically overexpressed in high-grade UC tissues compared with low-grade UC tissues. CUL1 up-regulation in recurrence cases in comparison with the non-recurrence cases. CUL1 expression upregulated in human UC tissues versus NCTs. CUL1 protein expression associated with androgen receptor. CONCLUSIONS: Our results demonstrate that increased CUL1 expression is significantly correlated with poor prognosis of patients with UC. CUL1 might be an important marker and a therapeutic target for UC.
Subject(s)
Carcinoma, Transitional Cell/genetics , Carcinoma, Transitional Cell/pathology , Cullin Proteins/genetics , Urinary Bladder Neoplasms/genetics , Urinary Bladder Neoplasms/pathology , Adult , Aged , Aged, 80 and over , Female , Gene Expression Regulation, Neoplastic , Humans , Male , Middle Aged , Neoplasm GradingABSTRACT
AIMS: Metabolic alterations in cancer, including bladder cancer, have been addressed in recent years. We aimed to study the role of phosphofructokinase (PFK) in muscle-invasive bladder cancer (MIBC). METHOD: By in silico analysis of the bladder cancer data from the Cancer Genome Atlas (TCGA) database using the cBioPortal platform, we studied genetic alteration of genes within the PFK family (PFKL, PFKM, PFKP, PFKFB1, PFKFB2, PFKFB3, and PFKFB4). In vitro studies were carried out using the PFK inhibitor 2,5-anhydro-D-glucitol-6-phosphate. RESULTS: Genetic alterations of PFK family genes were observed in ~44% of MIBC cases in TCGA. The main alterations were amplification and upregulation. Patients with altered PFK gene status were more likely to have a history of noninvasive bladder cancer. Altered PFK status was not associated with survival or disease relapse. Use of the PFK inhibitor significantly decreased the level of glycolysis and inhibited the growth and invasion of bladder cancer cells. CONCLUSIONS: PFKs were critical genes in charge of glycolysis and were upregulated in bladder cancer. Targeting this pathway could inhibit cell growth in bladder cancer.
