Program

Poster Presentations

Day 4, May 18（Fri.）　　Poster

4P-38　　PDF

EGFR Interactome Reveals Multiple Pathways and Regulatory Mechanism of Drug-resistance in Non-Small Cell Lung Cancer

(¹Genome and Systems Biology Degree Program, ²Institute of Chemistry, ³Department of Chemistry, ⁴Institute of Medical Genomics and Proteomics, ⁵Doctoral Degree Program of Translational Medicine)
^oPei-shan Wu^1,2, Miao-hsia Lin², Yu-ju Chen^1,2,3, Szu-hua Pan^1,4,5

The acquired secondary mutation of EGFR induced by TKI-therapy has been reported as the major factor of drug-resistance in NSCLC patients. EGFR regulates cancer pathogenesis by homo-/hetero-dimerization with EGFR family members, followed by complex interactions to recruit downstream associated proteins to subsequently activate its signaling pathways. It is intriguing to study whether the mutant-EGFR (mtEGFR) may recruit different interacting partners and alter downstream signaling. Two groups of NSCLC cells with primary/secondary EGFR mutation were used as drug sensitive/resistant models. AP-MS was applied to map the different mtEGFR protein-protein interactions. The candidate EGFR-binding proteins were stringently filtered by quantitative comparison with control group and elimination of non-specific binding in CRAPome. The results revealed that around 100 proteins were confidently identified to represent potential mtEGFR-binding partners. Bioinformatics revealed endocytosis which is responsible for vesicle formation and protein degradation potentially crucial for drug-resistance caused by T790M-mutation. We suggest that the regulation of EGFR-trafficking may provide survival advantage and resistance of therapy for cancer cell. Next, we start to clarify the biological function of targeted interactor/pathway involved in TKI-resistant mechanism. The knowledge of these results may provide novel treatment to overcome drug-resistance and tumor relapse in lung cancer therapeutic strategy.