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SOFT file
| Title / Description |
Genome-wide analysis of EGFR inhibitor erlotinib treatment in Head and neck, squamous cell carcinoma's FADU, SQ20B and Cal 27 |
| Accession |
GSE45891
|
| Summary |
Chronic inflammation plays a significant role in tumor promotion, migration and invasion. Using microarray analysis, we observed a profound increase in genes involved in pro-inflammatory pathways in epidermal growth factor receptor inhibitor (EGFRI)-treated head and neck squamous cell carcinoma (HNSCC) cell lines compared to their respective vehicle-treated cell lines. We hypothesized that the efficacy of EGFRIs may be offset by the pro-inflammatory response that these drugs produce in HNSCC tumor cells. We found that clinical EGFRIs such as erlotinib, cetuximab, lapatinib and panitumumab induced the secretion of pro-inflammatory cytokines such as IL-2, IL-4, IL-6, IL-8, GM-CSF, TNFα and IFNγ. Focusing on IL-6, we found that erlotinib induced a time-dependent increase in IL-6 mRNA and protein expression and exogenous IL-6 was able to protect HNSCC cells from erlotinib-induced cytotoxicity. Conversely, an IL-6 receptor antagonist tocilizumab, sensitized HNSCC cells to erlotinib in vitro and in vivo. Inhibitors of NFκB, p38 and JNK suppressed erlotinib-induced IL-6 expression, suggesting an important role of NFκB and MAPK pathways in IL-6 expression. Furthermore, knockdown of NADPH oxidase 4 (NOX4) suppressed erlotinib-induced pro-inflammatory cytokines expression. Taken together, these results suggest that clinical EGFRIs induce the expression of pro-inflammatory cytokines via NOX4. Therefore, the anti-tumor activity of EGFRIs may be partially reduced by activation of NOX4-mediated pro-inflammatory pathways in HNSCC. |
| Organism |
Homo sapiens |
| Platform |
GPL10558 |
| Normalized |
False |
| Parsed SOFT file |
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Metadata
| Differential expression method |
Characteristic Direction
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| Cutoff |
500 |
| Cell_type |
SQ20B |
| Drug_id |
DB00530 |
| Drug_name |
Erlotinib - 5uM - 48hr |
| Organism |
Human |
Visualizations
| Principal Component Analysis |
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| Hierarchical clustering |
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External Links and Downloads
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Gene lists
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Enrichr
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L1000CDS2
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PAEA
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Crowdsourcing |
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