Tid1-S regulates the mitochondrial localization of EGFR in non-small cell lung carcinoma.

The epidermal growth factor receptor (EGFR) is the major driver of non-small cell lung carcinoma (NSCLC). Mitochondrial accumulation of EGFR has been shown to promote metastasis in NSCLC, yet little is known about how the mitochondrial localization of EGFR is regulated. In this work, we show that Tid1 (also known as mitochondrial HSP40) is involved in the mitochondrial localization of EGFR, and that the DnaJ domain of Tid1-S is essential for the Tid1-S-mediated transportation of EGFR into mitochondria. Overexpression of Tid1-S increased the migration and invasion of NSCLC cells cultured in vitro. High levels of EGFR and Tid1-S were detected in the mitochondria of cancerous lesions from stage IV NSCLC patients, and high levels of mitochondrial Tid1-S/EGFR were correlated with lymph node metastasis and poor overall survival of NSCLC patients. We thus conclude that Tid1-S critically governs the mitochondrial localization of EGFR through the mtHSP70 transportation pathway, and that the mitochondrial accumulation of EGFR appears to promote metastasis in NSCLC.