Abstract A59: Exploration of Tid1 and mitochondrial EGFR in non-small cell lung carcinoma tumorgenesis

Abstract

Abstract The epidermal growth factor receptor (EGFR) over activity has been associated with a number of cancers, including non-small cell lung carcinoma (NSCLC). Known the critical role of EGFR in NSCLC and the recent findings that mitochondrial accumulation of EGFR could contribute to tumorigenesis, several interesting oncology questions related with the intracellular trafficking of EGFR to mitochondria need to be addressed. Tid1 (also known a mitochondrial Hsp40) has 2 isoforms, Tid1-L and Tid1-S, which may function differently. Since we have recently shown that Tid1 can interact with EGFR and that Tid1 is a mitochondrial protein, we postulate that Tid1 may participate in the mitochondrial localization of EGFR and play a role in NSCLC tumorigenesis. Using immunofluorescence microscopy, we observed that EGFR and Tid1 co-located within mitochondria in NSCLC cells. Moreover, mitochondria EGFR (mtEGFR) interact with both Tid1 isoforms directly under EGF stimulation, although there is a stronger association with the Tid1-S. In NSCLC patient tumors have shown mtEGFR and Tid1-S to be an indicator for poor clinical outcomes in cancer patients. Moreover, EGFR mitochondrial translocation can be decreased by erlotinib treatment in H3255 cells and greatly decline of cell viability. From the above observations, we believe that an adequate quantity of mitochondrial EGFR is critical for survival in NSCLC. Additional experiments are needed to further explore if Tid1 plays a role in the mitochondrial accumulation of EGFR in NSCLC cells. Citation Format: Chi-Yuan Chen, Yu-Han Lin, Wen-Chieh Pi. Exploration of Tid1 and mitochondrial EGFR in non-small cell lung carcinoma tumorgenesis. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2015 Nov 5-9; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2015;14(12 Suppl 2):Abstract nr A59.