Abstract
Among various heterogeneous types of bladder tumors, urothelial carcinoma is the most prevalent lesion. Some of the urinary bladder urothelial carcinomas (UBUCs) develop local recurrence and may cause distal invasion. Galectin-1 de-regulation significantly affects cell transformation, cell proliferation, angiogenesis, and cell invasiveness. In continuation of our previous investigation on the role of galectin-1 in UBUC tumorigenesis, in this study, proteomics strategies were implemented in order to find more galectin-1-associated signaling pathways. The results of this study showed that galectin-1 knockdown could induce 15 down-regulated proteins and two up-regulated proteins in T24 cells. These de-regulated proteins might participate in lipid/amino acid/energy metabolism, cytoskeleton, cell proliferation, cell-cell interaction, cell apoptosis, metastasis, and protein degradation. The aforementioned dys-regulated proteins were confirmed by western immunoblotting. Proteomics results were further translated to prognostic markers by analyses of biopsy samples. Results of cohort studies demonstrated that over-expressions of glutamine synthetase, alcohol dehydrogenase (NADP+), fatty acid binding protein 4, and toll interacting protein in clinical specimens were all significantly associated with galectin-1 up-regulation. Univariate analyses showed that de-regulations of glutamine synthetase and fatty acid binding protein 4 in clinical samples were respectively linked to disease-specific survival and metastasis-free survival.
Highlights
The surfaces of bladders and ureters are mostly covered by urothelium
We found that the galectin-1 protein is correlated with urinary bladder urothelial carcinomas (UBUCs) cell invasive capability by regulating the MMP9 activity through the Ras–related C3 botulinum toxin substrate 1 (Rac1)–mitogen-activated protein kinase kinase kinase 4 (MEKK4)–Jun N-terminal kinase (JNK)–Activator protein 1 (AP1) signaling pathway [24]
We exploited proteomics to find more novel molecular pathways evoked by galectin-1 dysregulation in UBUC cells, which might be related to UBUC carcinogenesis
Summary
The surfaces of bladders and ureters are mostly covered by urothelium. Among various heterogeneous types of bladder tumors, urothelial carcinoma is the most prevalent lesion. Urinary bladder urothelial carcinoma (UBUC) is often recognized as non-invasively papillary or superficially invasive tumors [1]. Some of the aforementioned tumors develop local recurrence and may cause distal invasion [1]. Galectin-1 is one of the fifteen mammalian proteins belonging to the β-galactoside binding family. It is a 14-kDa monomer with one carbohydrate-binding domain and usually forms a non-covalent homodimer in the cells [2]. The galectin-1 protein expression is precisely controlled by the methylation degree of the LGALS1 gene promoter located on chromosome 22q12 [3]
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