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Y. Kim
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P1.04 - Poster Session/ Biology, Pathology, and Molecular Testing (ID 233)
- Event: WCLC 2015
- Type: Poster
- Track: Biology, Pathology, and Molecular Testing
- Presentations: 1
- Moderators:
- Coordinates: 9/07/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P1.04-071 - Inhibition of EGFR Lysosomal Degradation in Lung Adenocarcinoma by Ubiquitin-Specific Protease 8 and Stratifin (ID 475)
09:30 - 17:00 | Author(s): Y. Kim
- Abstract
Background:
The epidermal growth factor receptor (EGFR) is one of the best-known targets of therapy for non-small cell lung cancer (NSCLC). Our purpose was to investigate whether ubiquitin-specific protease 8 (USP8) and stratifin (14-3-3σ or SFN) inhibit or stimulate lysosomal degradation of EGFR in lung adenocarcinoma.
Methods:
Using Western blotting and immunofluorescence analysis, we examined the effect of USP8 or SFN knockdown by siRNA and overexpression of USP8. Expressions of USP8 and SFN in normal and tumorous lung tissue were examined by Western blotting and immunohistochemistry.
Results:
USP8 or SFN knockdown led to downregulation of cellular proliferation, receptor tyrosine kinases such as EGFR and proto-oncogenes (c-Met), and downstream signaling pathways such as the AKT, ERK, and STAT3 pathways, whereas it upregulated the accumulation of EGFR at lysosomes for degradation. However, overexpression of USP8 led to an increase of EGFR and downstream signaling after EGF stimulation. Moreover, USP8 and SFN expressions were increased in the tumorous lung tissue in comparison with normal lung tissue from the same patient.
Conclusion:
USP8 and SFN inhibit ubiquitination of EGFR for lysosomal degradation in lung adenocarcinoma cells, suggesting that USP8 and SFN could be potential therapeutic targets for NSCLC.
