ROS1 oncogene orchestrates mitochondrial stress to cell metabolism, tumor microenvironment and metastasis in oral squamous cell carcinoma Yu-Jung Chang1, Line Chen1,2, 1Institute of Molecular Medicine, National Tsing Hua University, Hsinchu, Taiwan, ROC; 2Department of Medical Science, National Tsing Hua University, Hsinchu, Taiwan, ROC
Oral squamous cell carcinoma (OSCC) ranks as the sixth most common cancer in the world. The risk factors of OSCCs include tobacco and betel nut chewing, alcohol drinking, chronic inflammation and viral infections. Betel nut chewing is a main cause for oral cancer incidence in Taiwan. Surgery, radiation therapy, chemotherapy and anti-epidermal growth factor receptor (EGFR) therapy are major treatment for OSCC patients, but these are not effective for late-stage metastatic tumors. Therefore, the average 5-year survival rate is below 50% for Stage III-IV OSCC patients. Aberrant expressions of oncogenes are known to contribute to the progression of cancers. We have identified ROS1 oncogene, a receptor tyrosine kinase, of which expression is increased in the highly invasive OSCC cells and is required for OSCC metastasis. Recently, we demonstrate that mitochondria undergo fission/fragmentation in highly invasive OSCC cells. Interestingly, inhibiting or knocking down ROS1 reduces the fragmented phenotype of mitochondria and affects the mitochondrial stress. Evidence suggests that mitochondrial stress contribute to the pathogenesis of cancers. Our data further reveal a potential mechanism that the ROS1 oncogene-mediated mitochondrial stress results in cellular metabolic changes and remodeling the tumor microenvironment. These findings provide the new role of ROS1 oncogene, which orchestrates mitochondrial stress to metastasis in OSCC.
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