|
| Status |
Public on May 01, 2018 |
| Title |
Polyol pathway links glucose metabolism to the aggressiveness of cancer cells |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
Cancer cells alter their metabolism to support their malignant properties. By transcriptomic analysis we identified the glucose-transforming polyol pathway (PP) gene aldo-keto-reductase-1-member-B1 (AKR1B1) as strongly correlated with epithelial-to-mesenchymal transition (EMT). This association was confirmed staining samples from lung cancer patients and from an EMT-driven colon cancer mouse model with p53 deletion. In vitro, mesenchymal-like cancer cells showed increased AKR1B1 levels and AKR1B1 knockdown was sufficient to revert EMT. An equivalent level of EMT suppression was measured by targeting the downstream enzyme sorbitol-dehydrogenase (SORD), further pointing at the involvement of the PP. Comparative RNA sequencing profiling confirmed a profound alteration of EMT in PP-deficient cells, revealing a strong repression of TGF-Beta signature genes. Mechanistically, excess glucose was found to promote EMT through autocrine TGF-Beta stimulation, while PP-deficient cells were refractory to glucose-induced EMT. PP represents a molecular link between glucose metabolism and cancer differentiation and aggressiveness, and a novel potential therapeutic target.
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| |
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| Overall design |
3x3 biological replicated samples; 2 groups of samples with shRNA-mediated specific gene inhibition and scrambled control cells
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| |
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| Contributor(s) |
Ceppi P, Ekici AB |
| Citation(s) |
29343522 |
| |
| Submission date |
Oct 25, 2017 |
| Last update date |
May 15, 2019 |
| Contact name |
Arif B Ekici |
| E-mail(s) |
arif.ekici@uk-erlangen.de
|
| Organization name |
Institute of Human Genetics
|
| Street address |
Schwabachanlage 10
|
| City |
Erlangen |
| ZIP/Postal code |
91054 |
| Country |
Germany |
| |
|
| Platforms (1) |
| GPL16791 |
Illumina HiSeq 2500 (Homo sapiens) |
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| Samples (9)
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| Relations |
| BioProject |
PRJNA415806 |
| SRA |
SRP121474 |
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