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Proteomic analysis of pancreatic cancer stem cells: Functional role of fatty acid synthesis and mevalonate pathways
- Source :
- JOURNAL OF PROTEOMICS
- Publication Year :
- 2016
-
Abstract
- Recently, we have shown that the secretome of pancreatic cancer stem cells (CSCs) is characterized by proteins that participate in cancer differentiation, invasion, and metastasis. However, the differentially expressed intracellular proteins that lead to the specific characteristics of pancreatic CSCs have not yet been identified, and as a consequence the deranged metabolic pathways are yet to be elucidated. To identify the modulated proteins of pancreatic CSCs, iTRAQ-based proteomic analysis was performed to compare the proteome of Panc1 CSCs and Panc1 parental cells, identifying 230 modulated proteins. Pathway analysis revealed activation of glycolysis, the pentose phosphate pathway, the pyruvate-malate cycle, and lipid metabolism as well as downregulation of the Krebs cycle, the splicesome and non-homologous end joining. These findings were supported by metabolomics and immunoblotting analysis. It was also found that inhibition of fatty acid synthase by cerulenin and of mevalonate pathways by atorvastatin have a greater anti-proliferative effect on cancer stem cells than parental cells. Taken together, these results clarify some important aspects of the metabolic network signature of pancreatic cancer stem cells, shedding light on key and novel therapeutic targets and suggesting that fatty acid synthesis and mevalonate pathways play a key role in ensuring their viability. Biological significance To better understand the altered metabolic pathways of pancreatic cancer stem cells (CSCs), a comprehensive proteomic analysis and metabolite profiling investigation of Panc1 and Panc1 CSCs were carried out. The findings obtained indicate that Panc1 CSCs are characterized by upregulation of glycolysis, pentose phosphate pathway, pyruvate-malate cycle, and lipid metabolism and by downregulation of Krebs cycle, spliceosome and non-homologous end joining. Moreover, fatty acid synthesis and mevalonate pathways are shown to play a critical contribution to the survival of pancreatic cancer stem cells. This study is helpful for broadening the knowledge of pancreatic cancer stem cells and could accelerate the development of novel therapeutic strategies.
- Subjects :
- 0301 basic medicine
cancer stem cells
Proteomics
pancreatic cancer
Biophysics
pancreatic ductal adenocarcinoma
Mevalonic Acid
Biology
Biochemistry
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Downregulation and upregulation
Cancer stem cell
Pancreatic cancer
Cell Line, Tumor
medicine
Humans
Metabolomics
Glycolysis
Pancreas
Fatty acid synthesis
PDAC
Fatty Acids
medicine.disease
Cell biology
Cerulenin
Pancreatic Neoplasms
Metabolic pathway
030104 developmental biology
chemistry
030220 oncology & carcinogenesis
Metabolome
Neoplastic Stem Cells
Stem cell
Fatty Acid Synthases
Metabolic Networks and Pathways
Carcinoma, Pancreatic Ductal
Subjects
Details
- ISSN :
- 18767737
- Volume :
- 150
- Database :
- OpenAIRE
- Journal :
- Journal of proteomics
- Accession number :
- edsair.doi.dedup.....fdb877b03791ce1826d93a0aef48330c